Submissions for variant NM_001148.6(ANK2):c.669+3A>G

gnomAD frequency: 0.00072  dbSNP: rs370475820

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000170647	SCV000223199	uncertain significance	not provided	2017-10-04	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the ANK2 gene. The c.669+3 A>G variant has not been published as pathogenic or reported as a benign to our knowledge. This variant was observed in 48/24030 (0.2%) alleles from individuals of African background in large population cohorts (Lek et al., 2016). The c.669+3 A>G variant has been seen both independently, and in conjunction with additional cardiogenetic variants, in other individuals referred for arrhythmia genetic testing at GeneDx, although no informative segregation data are available. Moreover, no other splice site variants in the ANK2 gene have been reported in the Human Gene Mutation Database in association with LQTS (Stenson et al., 2014). Nevertheless, the c.669+3 A>G variant is predicted to destroy or significantly reduce the natural splice donor site in intron 6 and may cause abnormal gene splicing; however, in the absence of functional mRNA studies, the physiological consequence of this variant cannot be precisely determined.
Invitae	RCV001084450	SCV000254721	likely benign	Long QT syndrome	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620104	SCV000735401	likely benign	Cardiovascular phenotype	2018-11-07	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.