Variant Annotation
Available parameters and response documentation is available here
GET /lookup/7-151945072--T?add-ACMG-annotation=1
{
"chromosome": "chr7",
"alt": "T",
"ref": "",
"pos": 151945072,
"variant_id": "10190071519450720005",
"regions": {
"uniprot_regions": {
"version": "04-Oct-2024",
"items": [
{
"absolute_positon": 2623199191,
"amino_acid": "M1-K54,K54-E84,E84-S130,S130-K197,K197-G247,G247-E283,R284-S338,S338-K395,K395-K433,N434-R490,R490-D541,D541-A579,A579-V605,V605-Q844,G845-V884,G885-G923,V924-Q957,D958-K992,I993-W1053,W1053-R1108,R1108-V1145,V1145-D1167,D1167-E1238,E1238-G1281...",
"chromo": "chr7",
"colour": "255,0,0",
"description": null,
"length": 301079,
"position": 151832010,
"protein": "KMT2C_HUMAN",
"type": "homo_sapiens proteome sequences",
"pub_med_references": null
}
]
}
},
"variant_type": "Insertion",
"cytobands": "7q36.1",
"refseq_transcripts": [
{
"items": [
{
"name": "NM_170606.3",
"strand": "-",
"coding_impact": "nonsense",
"function": [
"NMD",
"coding"
],
"hgvs": "c.2447dup",
"hgvs_p1": "Y816*",
"hgvs_p3": "p.(Tyr816Ter)",
"location": "exon 14 of 59 before position 635 of 719",
"coding_location": "816 of 4912",
"canonical": true,
"gene_symbol": "KMT2C",
"splice_distance": "-86",
"ensembl_support_level": null,
"ensembl_appris": null,
"mane_select": "ENST00000262189.11",
"mane_plus": null,
"uniprot_id": null
}
],
"version": "224"
}
],
"ensembl_transcripts": [
{
"items": [
{
"name": "ENST00000262189.6",
"strand": "-",
"coding_impact": "nonsense",
"function": [
"NMD",
"coding"
],
"hgvs": "c.2447dup",
"hgvs_p1": "Y816*",
"hgvs_p3": "p.(Tyr816Ter)",
"location": "exon 14 of 59 before position 635 of 719",
"coding_location": "816 of 4912",
"canonical": true,
"gene_symbol": "KMT2C",
"splice_distance": "-86",
"ensembl_support_level": "1",
"ensembl_appris": "principal2",
"mane_select": "NM_170606.3",
"mane_plus": null,
"uniprot_id": "Q8NEZ4"
},
{
"name": "ENST00000355193.2",
"strand": "-",
"coding_impact": "nonsense",
"function": [
"NMD",
"coding"
],
"hgvs": "c.2447dup",
"hgvs_p1": "Y816*",
"hgvs_p3": "p.(Tyr816Ter)",
"location": "exon 14 of 60 before position 635 of 719",
"coding_location": "816 of 4969",
"canonical": false,
"gene_symbol": "KMT2C",
"splice_distance": "-86",
"ensembl_support_level": null,
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": "Q8NEZ4"
},
{
"name": "ENST00000418673.1",
"strand": "-",
"coding_impact": "nonsense",
"function": [
"NMD",
"coding"
],
"hgvs": "c.32dup",
"hgvs_p1": "Y11*",
"hgvs_p3": "p.(Tyr11Ter)",
"location": "exon 1 of 6 before position 34 of 118",
"coding_location": "11 of 227",
"canonical": false,
"gene_symbol": "KMT2C",
"splice_distance": "-86",
"ensembl_support_level": "5",
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
},
{
"name": "ENST00000558084.1",
"strand": "-",
"coding_impact": null,
"function": [
"non-coding exon"
],
"hgvs": null,
"hgvs_p1": null,
"hgvs_p3": null,
"location": "exon 14 of 59 before position 635 of 719",
"coding_location": null,
"canonical": false,
"gene_symbol": "KMT2C",
"splice_distance": "-86",
"ensembl_support_level": null,
"ensembl_appris": null,
"mane_select": null,
"mane_plus": null,
"uniprot_id": null
}
],
"version": "112"
}
],
"gnomad_exomes": [
{
"version": "2.1.1",
"filter": "InbreedingCoeff;RF",
"ac": 81747,
"an": 167790,
"af": 0.48719828356874667,
"ac_afr": 3538,
"ac_amr": 11304,
"ac_asj": 3268,
"ac_eas": 6142,
"ac_eas_kor": 1169,
"ac_eas_jpn": 59,
"ac_eas_oea": 4914,
"ac_fin": 7706,
"ac_nfe": 38135,
"ac_nfe_bgr": 993,
"ac_nfe_est": 93,
"ac_nfe_nwe": 13432,
"ac_nfe_onf": 10619,
"ac_nfe_seu": 3882,
"ac_nfe_swe": 9116,
"ac_oth": 1883,
"ac_sas": 9771,
"ac_afr_male": 1341,
"ac_amr_male": 4636,
"ac_asj_male": 1671,
"ac_eas_male": 3014,
"ac_fin_male": 4014,
"ac_nfe_male": 21421,
"ac_oth_male": 970,
"ac_sas_male": 7438,
"ac_afr_female": 2197,
"ac_amr_female": 6668,
"ac_asj_female": 1597,
"ac_eas_female": 3128,
"ac_fin_female": 3692,
"ac_nfe_female": 16714,
"ac_oth_female": 913,
"ac_sas_female": 2333,
"ac_male": 44505,
"ac_female": 37242,
"an_afr": 7504,
"an_amr": 23102,
"an_asj": 6766,
"an_eas": 12322,
"an_eas_kor": 2350,
"an_eas_jpn": 118,
"an_eas_oea": 9854,
"an_fin": 15734,
"an_nfe": 78650,
"an_nfe_bgr": 2018,
"an_nfe_est": 192,
"an_nfe_nwe": 28022,
"an_nfe_onf": 21774,
"an_nfe_seu": 8030,
"an_nfe_swe": 18614,
"an_oth": 3936,
"an_sas": 19776,
"an_afr_male": 2848,
"an_amr_male": 9490,
"an_asj_male": 3466,
"an_eas_male": 6050,
"an_fin_male": 8194,
"an_nfe_male": 44160,
"an_oth_male": 2022,
"an_sas_male": 15044,
"an_afr_female": 4656,
"an_amr_female": 13612,
"an_asj_female": 3300,
"an_eas_female": 6272,
"an_fin_female": 7540,
"an_nfe_female": 34490,
"an_oth_female": 1914,
"an_sas_female": 4732,
"an_male": 91274,
"an_female": 76516,
"age_hist_het_under_30": 1591,
"age_hist_het_30_35": 2238,
"age_hist_het_35_40": 2966,
"age_hist_het_40_45": 5541,
"age_hist_het_45_50": 6766,
"age_hist_het_50_55": 8176,
"age_hist_het_55_60": 7573,
"age_hist_het_60_65": 6858,
"age_hist_het_65_70": 5847,
"age_hist_het_70_75": 3942,
"age_hist_het_75_80": 2726,
"age_hist_het_over_80": 1319,
"variant_type": "mixed",
"segdup": true,
"original_variant": "7-151945071-G-GT",
"main_data": "ƒ = 0.487"
}
],
"gnomad_exomes_coverage": [
{
"version": "2.1",
"coverage_mean": [
99.37200164794922
],
"coverage_median": [
100.0
],
"coverage_20_frequency": [
1.0
]
}
],
"gnomad_genomes": [
{
"version": "2.1.1",
"filter": "InbreedingCoeff",
"ac": 10703,
"an": 22162,
"af": 0.4829437776373973,
"ac_afr": 2353,
"ac_amr": 311,
"ac_asj": 98,
"ac_eas": 633,
"ac_fin": 1243,
"ac_nfe": 5677,
"ac_nfe_est": 1714,
"ac_nfe_nwe": 3153,
"ac_nfe_onf": 781,
"ac_nfe_seu": 29,
"ac_oth": 388,
"ac_afr_male": 1372,
"ac_amr_male": 152,
"ac_asj_male": 70,
"ac_eas_male": 424,
"ac_fin_male": 591,
"ac_nfe_male": 3171,
"ac_oth_male": 176,
"ac_afr_female": 981,
"ac_amr_female": 159,
"ac_asj_female": 28,
"ac_eas_female": 209,
"ac_fin_female": 652,
"ac_nfe_female": 2506,
"ac_oth_female": 212,
"ac_male": 5956,
"ac_female": 4747,
"an_afr": 4982,
"an_amr": 634,
"an_asj": 198,
"an_eas": 1272,
"an_fin": 2564,
"an_nfe": 11714,
"an_nfe_est": 3496,
"an_nfe_nwe": 6530,
"an_nfe_onf": 1628,
"an_nfe_seu": 60,
"an_oth": 798,
"an_afr_male": 2914,
"an_amr_male": 308,
"an_asj_male": 142,
"an_eas_male": 852,
"an_fin_male": 1216,
"an_nfe_male": 6566,
"an_oth_male": 368,
"an_afr_female": 2068,
"an_amr_female": 326,
"an_asj_female": 56,
"an_eas_female": 420,
"an_fin_female": 1348,
"an_nfe_female": 5148,
"an_oth_female": 430,
"an_male": 12366,
"an_female": 9796,
"age_hist_het_under_30": 1536,
"age_hist_het_30_35": 433,
"age_hist_het_35_40": 480,
"age_hist_het_40_45": 673,
"age_hist_het_45_50": 955,
"age_hist_het_50_55": 1200,
"age_hist_het_55_60": 931,
"age_hist_het_60_65": 736,
"age_hist_het_65_70": 495,
"age_hist_het_70_75": 280,
"age_hist_het_75_80": 123,
"age_hist_het_over_80": 51,
"variant_type": "mixed",
"segdup": true,
"original_variant": "7-151945071-G-GT",
"main_data": "ƒ = 0.483"
}
],
"gnomad_genomes_coverage": [
{
"version": "2.1",
"coverage_mean": [
92.58300018310547
],
"coverage_median": [
100.0
],
"coverage_20_frequency": [
1.0
]
}
],
"ncbi_clinvar2": [
{
"version": "04-Oct-2024",
"review_status": "criteria provided, single submitter",
"review_stars": 1,
"variation_id": 403020,
"num_submitters": 2,
"pub_med_references": null,
"clinical_significance": [
"Benign"
],
"last_evaluation": "20240623",
"origin": null,
"accessions": [
{
"variation_id": 403020,
"accession_id": "RCV001251811",
"review_status": "no assertion criteria provided",
"allele_id": 390552,
"review_description": "Likely benign",
"clinical_significance": [
"Likely benign"
],
"date_created": 20200815,
"title": "NM_170606.3(KMT2C):c.2447dup (p.Tyr816Ter) AND Intellectual disability",
"variant_id": 10190071519450720005,
"review_date": 20190101,
"review_stars": 0,
"finding": [
{
"normalized_phenotype": [
"Intellectual Disability"
],
"symbols": {
"medgen": "C3714756",
"mesh": "D008607",
"mondo": "MONDO:0001071",
"human_phenotype_ontology": "HP:0007180"
},
"names": [
"Intellectual Disability",
"Intellectual Functioning Disability",
"Intellectual Disability",
"Intellectual Developmental Disorder"
]
}
],
"submission_description": [],
"submissions": [
{
"review_description": "Likely benign",
"submitter_name": "Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille",
"submission_description": [],
"review_date": 20190101,
"method": "clinical testing",
"finding": [
{
"symbols": {
"hp": "HP:0001249"
},
"normalized_phenotype": [
"Intellectual Disability"
]
}
],
"origin": "inherited",
"date_updated": 20200815,
"submitter_date": 20200505,
"clinical_significance": [
"Likely benign"
],
"review_status": "no assertion criteria provided",
"accession_id": "SCV001427553"
}
]
},
{
"variation_id": 403020,
"accession_id": "RCV000455198",
"review_status": "criteria provided, single submitter",
"allele_id": 390552,
"review_description": "Benign",
"clinical_significance": [
"Benign"
],
"date_created": 20170410,
"diseases": [
{
"symbols": {
"medgen": "CN169374"
},
"names": [
"Not Specified",
"Allhighlypenetrant"
]
}
],
"review_date": 20160425,
"review_stars": 1,
"submission_description": [],
"submissions": [
{
"review_description": "Benign",
"submitter_name": "Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine",
"submission_description": [
"Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: frequency"
],
"review_date": 20160425,
"method": "clinical testing",
"diseases": [
{
"names": [
"Not Specified"
]
}
],
"origin": "germline",
"date_updated": 20170410,
"submitter_date": 20170403,
"clinical_significance": [
"Benign"
],
"review_status": "criteria provided, single submitter",
"accession_id": "SCV000539482"
}
],
"title": "NM_170606.3(KMT2C):c.2447dup (p.Tyr816Ter) AND not specified",
"variant_id": 10190071519450720005
}
],
"main_data": "benign **1**",
"names": [
"NM_170606.3(KMT2C):c.2447dup (p.Tyr816Ter)",
"p.Tyr816X"
],
"variant_type": "Duplication"
}
],
"publications": {
"publications": [
{
"referenced_by": [
"VarSome users"
],
"pub_med_id": 26014803
}
],
"genes": [
{
"publications": [
{
"referenced_by": [
"gene2phenotype"
],
"pub_med_id": 38146907
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 36360262
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 35685914
},
{
"referenced_by": [
"gene2phenotype"
],
"pub_med_id": 35324822
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 35108799
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 34958143
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 33619735
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 33482836
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 32366967
},
{
"referenced_by": [
"gene2phenotype"
],
"pub_med_id": 31712638
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 30847515
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 30564305
},
{
"referenced_by": [
"gene2phenotype",
"GenCC",
"PanelApp"
],
"pub_med_id": 29276005
},
{
"referenced_by": [
"gene2phenotype",
"GenCC",
"PanelApp",
"CGD",
"dbNSFP"
],
"pub_med_id": 29069077
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 28263302
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 28191890
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 26185613
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 26167905
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 26166478
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 25989142
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 25363768
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 25326635
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 25294932
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 24581740
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 24267887
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 24090431
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 23999528
},
{
"referenced_by": [
"GenCC"
],
"pub_med_id": 23375656
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 23042784
},
{
"referenced_by": [
"GenCC",
"PanelApp",
"CGD",
"dbNSFP"
],
"pub_med_id": 22726846
},
{
"referenced_by": [
"PanelApp"
],
"pub_med_id": 20212079
},
{
"referenced_by": [
"dbNSFP"
],
"pub_med_id": 17500065
}
],
"gene_symbol": "KMT2C",
"gene_id": 12315
}
]
},
"publication_counts": [
{
"type": "variant",
"id": "10190071519450720005",
"count": 2
},
{
"type": "gene",
"id": 12315,
"count": 343,
"symbol": "KMT2C"
}
],
"saphetor_known_pathogenicity": [
{
"version": "06-Nov-2024",
"items": [
{
"annotations": {
"NCBI ClinVar2": [
{
"functions": [
"NMD",
"coding"
],
"coding_impact": "nonsense",
"acmg_confirmed": false,
"acmg_class": "Benign",
"acmg_reannotated": "Likely Pathogenic",
"source": "NCBI ClinVar2",
"codon": 816,
"gene_symbol": "KMT2C",
"hgvs": "Y816*",
"transcript": "NM_170606.3",
"submission_count": 2,
"review_stars": 1,
"accession_count": 2,
"publication_count": 0,
"clinical_significance": [
"benign"
],
"disease_name": [
"Allhighlypenetrant",
"Intellectual Developmental Disorder",
"Intellectual Disability",
"Intellectual Functioning Disability",
"Not Specified"
]
}
],
"Saphetor PubMedUserEntry": [
{
"functions": [
"NMD",
"coding"
],
"coding_impact": "nonsense",
"acmg_confirmed": false,
"acmg_class": "Uncertain Significance",
"acmg_reannotated": "Likely Pathogenic",
"source": "Saphetor PubMedUserEntry",
"codon": 816,
"gene_symbol": "KMT2C",
"hgvs": "Y816*",
"transcript": "NM_170606.3",
"pub_med_references": [
26014803
],
"pathogenicity": "DA",
"id": 10096,
"confirmedByFunctionalStudy": false
}
]
}
}
]
}
],
"acmg_annotation": {
"version_name": "12.5.1",
"gene_symbol": "KMT2C",
"transcript": "NM_170606.3",
"transcript_reason": "MANE select",
"coding_impact": "nonsense",
"verdict": {
"ACMG_rules": {
"benign_score": 1,
"benign_subscore": "Likely Benign",
"clinical_score": 4.257,
"pathogenic_score": 8,
"pathogenic_subscore": "Likely Pathogenic",
"total_score": 7,
"verdict": "Likely Pathogenic"
},
"classifications": [
"PVS1",
"BP6"
]
},
"classifications": [
{
"name": "PVS1",
"met_criteria": true,
"user_explain": [
"Null variant (nonsense) in gene KMT2C, predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 139 reported pathogenic LOF variants). The exon contains 5 pathogenic variants. The truncated region contains 136 pathogenic variants."
]
},
{
"name": "BP6",
"met_criteria": true,
"user_explain": [
"Combined evidence strength is Supporting (score = 1).",
"Supporting: ClinVar classifies this variant as Benign, 1 star (reviewed Jun '24, 2 submissions of which 1 is from high confidence submitter)."
]
}
],
"gene_id": 12315,
"sample_findings": {
"phenotypes": "No matching phenotype found for gene KMT2C which is associated with Intellectual Disability, Intellectual Disability, Autosomal Dominant 40, Kleefstra Syndrome 2, Kleefstra Syndrome 2 617768 and 3 more, according to CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp and gene2phenotype.",
"mode_of_inheritance": "AD, based on gene information from CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp and gene2phenotype."
}
},
"phylop100way": [
{
"version": "13-Apr-2021",
"conservation_score": [
"0.907",
"4.789",
"6.663"
]
}
],
"maxentscan": null
}