Submissions for variant NM_001148.6(ANK2):c.11718G>A (p.Arg3906=)

gnomAD frequency: 0.00128  dbSNP: rs35724152

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000199294	SCV000252750	benign	Long QT syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000621817	SCV000735843	likely benign	Cardiovascular phenotype	2017-04-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000779696	SCV000916448	benign	not specified	2018-02-05	criteria provided, single submitter	clinical testing	Variant summary: ANK2 c.11718G>A alters a non-conserved nucleotide resulting in a synonymous change. Several computational tools predict a significant impact on normal splicing: Five predict the variant abolishes a cryptic exonic 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00042 in 276830 control chromosomes in gnomAD. The observed variant frequency is approximately 41.9 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.11718G>A in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and has classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001640298	SCV001857075	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002253284	SCV002525101	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003917803	SCV004735759	benign	ANK2-related disorder	2019-05-02	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).