1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAA
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate
The NM_001232.4(CASQ2):c.738-9_738-5delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,278,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Consequence
NM_001232.4 splice_region, intron
Scores
Clinical Significance
Conservation
Publications
- catecholaminergic polymorphic ventricular tachycardiaInheritance: AD, AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- catecholaminergic polymorphic ventricular tachycardia 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -2 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00 AC: 0AN: 114030Hom.: 0 Cov.: 0
GnomAD4 exome AF: 0.00242 AC: 3095AN: 1278340Hom.: 0 AF XY: 0.00247 AC XY: 1574AN XY: 636780 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
Age Distribution
GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 114000Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 52882
ClinVar
Submissions by phenotype
not specified Benign:3
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Variant summary: CASQ2 c.738-9_738-5delTTTTT 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. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 179292 control chromosomes (gnomAD). However, the variant is located in a homopolymer region of 20 Ts, which is a highly polymorphic region. Therefore, suggesting the region is tolerable to changes in length of poly Ts. To our knowledge, no occurrence of c.738-9_738-5delTTTTT in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Co-occurrence with another pathogenic variant has been observed in an internal LCA sample (PKP2 c.2197_2202delinsG , p.H733fsX8), providing supporting evidence for a benign role. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. -
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at