Submissions for variant NM_001148.6(ANK2):c.2277+9C>T

gnomAD frequency: 0.00205  dbSNP: rs141965666

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000227233	SCV000286235	benign	Long QT syndrome	2024-01-22	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000625120	SCV000447159	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	RCV000588231	SCV000697731	benign	not provided	2017-08-10	criteria provided, single submitter	clinical testing	Variant summary: The ANK2 c.2277+9C>T variant involves the alteration of a non-conserved intronic nucleotide. MutationTaster predicts a benign outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in the large control database ExAC at a frequency of 0.0030006 (359/119642 control chromosomes [2 homozygotes]), which is approximately 300 times the estimated maximal expected allele frequency of a pathogenic ANK2 variant (0.00001), strongly suggesting this variant is likely a benign polymorphism. In ClinVar, one clinical diagnostic laboratory classified this variant as benign (Invitae), while another classified this variant as uncertain significance (Illumina). 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.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625120	SCV000743817	likely benign	Cardiac arrhythmia, ankyrin-B-related	2017-07-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000588231	SCV001890531	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000625120	SCV002525008	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003937893	SCV004748585	benign	ANK2-related condition	2019-07-23	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV001699075	SCV001923774	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001699075	SCV001957869	benign	not specified		no assertion criteria provided	clinical testing