Submissions for variant NM_001148.6(ANK2):c.2127T>C (p.Asn709=)

gnomAD frequency: 0.00009  dbSNP: rs113454484

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000241638	SCV000320589	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.
Invitae	RCV000526592	SCV000627631	likely benign	Long QT syndrome	2023-11-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586523	SCV000697730	benign	not provided	2016-12-19	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.2127T>C (p.Asn709Asn) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 2/5 splice prediction tools predict that this variant may weaken a cryptic 5' splicing donor site, while 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SC35. However, these predictions have yet to be confirmed by functional studies. This variant was found in 8/120974 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0007703 (8/10386). This frequency is about 77 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. In addition, one clinical diagnostic laboratory classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
GeneDx	RCV000586523	SCV001944507	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV002253340	SCV002525004	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003939925	SCV004756718	likely benign	ANK2-related disorder	2021-04-02	criteria provided, single submitter	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).