ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.11119G>A (p.Asp3707Asn)

gnomAD frequency: 0.00013  dbSNP: rs199549660
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000170709 SCV000050642 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000170709 SCV000223262 uncertain significance not provided 2020-02-03 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27871843, 23861362, 30564305)
Invitae RCV001082474 SCV000752878 likely benign Long QT syndrome 2020-11-29 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health,University of California San Diego RCV000852558 SCV000995258 uncertain significance Supraventricular tachycardia 2017-10-02 criteria provided, single submitter clinical testing
Illumina Laboratory Services,Illumina RCV001144037 SCV001304611 likely benign Cardiac arrhythmia, ankyrin-B-related 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000185494 SCV001442714 benign not specified 2020-10-26 criteria provided, single submitter clinical testing Variant summary: ANK2 c.11119G>A (p.Asp3707Asn) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00033 in 251152 control chromosomes, predominantly at a frequency of 0.0017 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 255 fold of the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Long QT Syndrome phenotype (6.7e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One co-occurrence with another pathogenic variant has been internally reported (SCN5A c.5443_5446delTCTG, p.Ser1815ThrfsX18), providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (2x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as benign.

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