Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001148.6(ANK2):c.3893+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,600,286 control chromosomes in the GnomAD database, including 17,031 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
ANK2 (HGNC:493): (ankyrin 2) This gene encodes a member of the ankyrin family of proteins that link the integral membrane proteins to the underlying spectrin-actin cytoskeleton. Ankyrins play key roles in activities such as cell motility, activation, proliferation, contact and the maintenance of specialized membrane domains. Most ankyrins are typically composed of three structural domains: an amino-terminal domain containing multiple ankyrin repeats; a central region with a highly conserved spectrin binding domain; and a carboxy-terminal regulatory domain which is the least conserved and subject to variation. The protein encoded by this gene is required for targeting and stability of Na/Ca exchanger 1 in cardiomyocytes. Mutations in this gene cause long QT syndrome 4 and cardiac arrhythmia syndrome. Multiple transcript variants encoding different isoforms have been described. [provided by RefSeq, Dec 2011]
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 4-113339336-G-T is Benign according to our data. Variant chr4-113339336-G-T is described in ClinVar as [Benign]. Clinvar id is 136391.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-113339336-G-T is described in Lovd as [Benign].
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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Jun 14, 2012
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -
Cardiac arrhythmia, ankyrin-B-related Benign:2
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Dec 05, 2021
Genome-Nilou Lab
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
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not provided Benign:1
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Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided
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Long QT syndrome Benign:1
Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter