Submissions for variant NM_001148.6(ANK2):c.11181C>T (p.Gly3727=)

gnomAD frequency: 0.00009  dbSNP: rs185569619

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001087011	SCV000557188	benign	Long QT syndrome	2023-10-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590594	SCV000697721	benign	not provided	2017-01-30	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.11181C>T (p.Gly3727Gly) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 33/121348 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.001643 (19/11564). This frequency is about 164 times the estimated maximal expected allele frequency of a pathogenic ANK2 variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001144038	SCV001304612	benign	Cardiac arrhythmia, ankyrin-B-related	2018-03-28	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV001256866	SCV001433358	likely benign	not specified	2019-09-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000590594	SCV001832023	likely benign	not provided	2021-05-21	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001144038	SCV002525094	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002436485	SCV002748471	likely benign	Cardiovascular phenotype	2022-04-04	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen	RCV000590594	SCV004148763	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BP7