Submissions for variant NM_001148.6(ANK2):c.5313G>A (p.Lys1771=)

gnomAD frequency: 0.00009  dbSNP: rs140992864

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000246914	SCV000320593	likely benign	Cardiovascular phenotype	2015-12-24	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000542104	SCV000627652	likely benign	Long QT syndrome	2023-11-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590344	SCV000697738	benign	not provided	2016-12-19	criteria provided, single submitter	clinical testing	Variant summary: The c.5313G>A (p.Lys1771=) in ANK2 gene is a synonymous change that involves a non-conserved nucleotide. 4/5 programs in Alamut predict that this variant does not affect a normal splicing, however no functional studies supporting these predictions were published at the time of evaluation. The variant is present in the large control population dataset of ExAC at a frequency 0.000066 (8/121064 chrs tested), exclusively in individuals of African origin (0.00077; 8/10334 chrs tested). This frequency exceeds the estimated maximal expected allele frequency of a pathogenic variant in ANK2 gene (0.00001). The c. 5313G>A has not, to our knowledge, been reported in affected individuals via published reports, but is cited as Likely Benign by a reputable database/clinical laboratory. The variant seems to be an ethnic specific polymorphism, therefore it has been classified as Benign.
Genome-Nilou Lab	RCV002253342	SCV002525047	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000590344	SCV004148733	likely benign	not provided	2022-10-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003947820	SCV004760279	likely benign	ANK2-related disorder	2021-04-02	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).