Submissions for variant NM_001148.6(ANK2):c.4152T>C (p.Asp1384=)

gnomAD frequency: 0.00267  dbSNP: rs116128106

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000229379	SCV000286247	benign	Long QT syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001094842	SCV000447177	likely benign	Cardiac arrhythmia, ankyrin-B-related	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587944	SCV000697725	benign	not provided	2016-04-04	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.4152T>C variant affects a non-conserved nucleotide, resulting in no amino acid change. Although Mutation Taster predicts damaging outcome for this variant, 5/5 Alamut algorithms predict no change to splicing. This variant was found in 177/121352 control chromosomes at a frequency of 0.0014586, which is about 146 times the maximal expected allele frequency for a pathogenic ANK2 variant (0.00001), suggesting this variant is benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as benign.
Ambry Genetics	RCV000620820	SCV000737431	likely benign	Cardiovascular phenotype	2016-12-21	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587944	SCV000885009	benign	not provided	2017-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000587944	SCV001944509	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001094842	SCV002525041	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587944	SCV004148728	likely benign	not provided	2023-04-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BP7, BS2
Clinical Genetics, Academic Medical Center	RCV001699257	SCV001922368	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699257	SCV001927825	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699257	SCV001952701	benign	not specified		no assertion criteria provided	clinical testing