Submissions for variant NM_001148.6(ANK2):c.2178+18C>T

gnomAD frequency: 0.00674  dbSNP: rs45447896

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000625119	SCV000743816	benign	Cardiac arrhythmia, ankyrin-B-related	2014-10-09	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001613411	SCV001157543	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001000575	SCV001448505	benign	not specified	2020-11-02	criteria provided, single submitter	clinical testing	Variant summary: ANK2 c.2178+18C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0023 in 249380 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 338- fold the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Long QT Syndrome phenotype (6.7e-06), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2178+18C>T in individuals affected with Long QT Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, citing the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001613411	SCV001836751	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002060695	SCV002405314	benign	Long QT syndrome	2025-01-29	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000625119	SCV002525006	benign	Cardiac arrhythmia, ankyrin-B-related	2021-12-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001613411	SCV005300339	benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV001000575	SCV001926169	benign	not specified		no assertion criteria provided	clinical testing