Submissions for variant NM_001148.6(ANK2):c.1401A>G (p.Ala467=)

gnomAD frequency: 0.00269  dbSNP: rs142159132

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000234501	SCV000286234	benign	Long QT syndrome	2024-01-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625118	SCV000447151	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	RCV000586416	SCV000697727	benign	not provided	2017-02-20	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.1401A>G (p.Ala467Ala) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect binding of ESE sites. These predictions have not been confirmed by functional studies. This variant was found in 99/23776 control chromosomes (including one homozygote) at a frequency of 0.0041639, which is approximately 416 times the estimated maximal expected allele frequency of a pathogenic ANK2 variant (0.00001), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory has classified this variant as benign. Taken together, this variant is classified as Benign.
Ambry Genetics	RCV000620406	SCV000737411	benign	Cardiovascular phenotype	2015-06-11	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625118	SCV000743815	benign	Cardiac arrhythmia, ankyrin-B-related	2016-11-04	criteria provided, single submitter	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000625118	SCV000745234	likely benign	Cardiac arrhythmia, ankyrin-B-related	2017-06-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000586416	SCV001944504	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000625118	SCV002524996	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000586416	SCV004034060	likely benign	not provided	2023-09-01	criteria provided, single submitter	clinical testing	ANK2: BP4, BP7, BS1
Clinical Genetics, Academic Medical Center	RCV001699256	SCV001925462	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699256	SCV001954663	benign	not specified		no assertion criteria provided	clinical testing