Submissions for variant NM_001148.6(ANK2):c.5985G>A (p.Lys1995=)

gnomAD frequency: 0.00095  dbSNP: rs116652427

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000251907	SCV000318699	likely benign	Cardiovascular phenotype	2017-01-04	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.
GeneDx	RCV000589398	SCV000527775	likely benign	not provided	2020-09-25	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086512	SCV000627659	benign	Long QT syndrome	2025-01-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000589398	SCV000697740	benign	not provided	2016-09-06	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.5985G>A (p.Lys1995Lys) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant, and 5/5 splicing algorithms predict no significant change to normal splicing. This variant was found in 29/120876 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0027855 (28/10052). This frequency is about 279 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 African 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.
Genome-Nilou Lab	RCV002253334	SCV002525051	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000589398	SCV004148737	benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	ANK2: BS1, BS2
Breakthrough Genomics, Breakthrough Genomics	RCV000589398	SCV005263144	likely benign	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV003947813	SCV004760946	likely benign	ANK2-related disorder	2019-02-19	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).