Submissions for variant NM_001148.6(ANK2):c.7132G>A (p.Glu2378Lys)

gnomAD frequency: 0.00222  dbSNP: rs141191319

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health	RCV000171744	SCV000050747	likely benign	not provided	2013-06-24	criteria provided, single submitter	research
Invitae	RCV001082214	SCV000218673	benign	Long QT syndrome	2024-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000171744	SCV000512039	likely benign	not provided	2020-11-10	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 26230511, 23861362, 23396983, 28465117)
Ambry Genetics	RCV000621823	SCV000735256	benign	Cardiovascular phenotype	2018-04-24	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625125	SCV000743825	likely benign	Cardiac arrhythmia, ankyrin-B-related	2014-10-09	criteria provided, single submitter	clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852972	SCV000995721	likely benign	Brugada syndrome	2018-02-27	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625125	SCV001310935	uncertain significance	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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000426638	SCV001426961	benign	not specified	2020-07-06	criteria provided, single submitter	clinical testing	Variant summary: ANK2 c.7132G>A (p.Glu2378Lys) 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 0.0023 in 250666 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 230-fold of the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.7132G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as benign (2x), likely benign (2x) or VUS. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV000171744	SCV004148744	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BS1
Clinical Genetics, Academic Medical Center	RCV000426638	SCV001918918	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000171744	SCV001952384	likely benign	not provided		no assertion criteria provided	clinical testing