Submissions for variant NM_001148.6(ANK2):c.7054_7059del (p.Gly2352_Gln2353del)

dbSNP: rs774514148

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000587816	SCV000342327	uncertain significance	not provided	2016-06-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587816	SCV000697745	uncertain significance	not provided	2016-02-22	criteria provided, single submitter	clinical testing	Variant summary: The c.7054_7059delGGTCAA variant leads to deletion of 6 nucleotides (deletion of Gly and Gln) in a non-repetitive region. One in-silico tool predicts benign outcome for this variant. 5/5 programs in Alamut predict that this variant does not affect normal splicing. ESE finder predicts that this variant may affect ESE site of SC35. However, these predictions are not confirmed by experimental studies. This variant is found in 13/121240 control chromosomes at a frequency of 0.0001072, which is about 11 times of maximal expected frequency of a pathogenic allele (0.00001), suggesting this variant is benign. However, the sequencing data in controls did not pass the quality filter, which puts the control allele frequency in doubt. Co-occurrence with a pathogenic variant (KCNH2, c.215C>A/p.P72Q) has been found in one sample in our laboratory. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/other clinical laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant was classified as VUS-possibly benign.
Invitae	RCV001045075	SCV001208905	uncertain significance	Long QT syndrome	2023-08-24	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 288266). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This variant is present in population databases (rs774514148, gnomAD 0.01%). This variant, c.7054_7059del, results in the deletion of 2 amino acid(s) of the ANK2 protein (p.Gly2352_Gln2353del), but otherwise preserves the integrity of the reading frame.
GeneDx	RCV000587816	SCV002104334	uncertain significance	not provided	2023-01-03	criteria provided, single submitter	clinical testing	In-frame deletion of two amino acids in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Located in exon 38, which is reported as being expressed in a brain-specific transcript (Otto et al, 1991; Cunha et al, 2008; Wu et al, 2015); Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 27535533)
Ambry Genetics	RCV002374476	SCV002667970	likely benign	Cardiovascular phenotype	2022-12-20	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.
Fulgent Genetics, Fulgent Genetics	RCV002487254	SCV002779994	uncertain significance	Cardiac arrhythmia, ankyrin-B-related	2021-07-16	criteria provided, single submitter	clinical testing
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille	RCV001252390	SCV001428145	likely benign	Intellectual disability	2019-01-01	no assertion criteria provided	clinical testing