rs10801999
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001232.4(CASQ2):c.226G>A(p.Val76Met) variant causes a missense change. The variant allele was found at a frequency of 0.00964 in 1,610,530 control chromosomes in the GnomAD database, including 824 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V76A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001232.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
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CASQ2 | ENST00000261448.6 | c.226G>A | p.Val76Met | missense_variant | Exon 1 of 11 | 1 | NM_001232.4 | ENSP00000261448.5 | ||
CASQ2 | ENST00000488931.2 | n.-51G>A | 5_prime_UTR_premature_start_codon_gain_variant | Exon 2 of 13 | 3 | ENSP00000518226.1 | ||||
CASQ2 | ENST00000488931.2 | n.-51G>A | non_coding_transcript_exon_variant | Exon 2 of 13 | 3 | ENSP00000518226.1 | ||||
CASQ2 | ENST00000488931.2 | n.-51G>A | 5_prime_UTR_variant | Exon 2 of 13 | 3 | ENSP00000518226.1 |
Frequencies
GnomAD3 genomes AF: 0.0144 AC: 2192AN: 152144Hom.: 87 Cov.: 32
GnomAD3 exomes AF: 0.0317 AC: 7968AN: 251022Hom.: 544 AF XY: 0.0262 AC XY: 3551AN XY: 135722
GnomAD4 exome AF: 0.00914 AC: 13332AN: 1458268Hom.: 736 Cov.: 30 AF XY: 0.00870 AC XY: 6313AN XY: 725764
GnomAD4 genome AF: 0.0144 AC: 2196AN: 152262Hom.: 88 Cov.: 32 AF XY: 0.0174 AC XY: 1292AN XY: 74448
ClinVar
Submissions by phenotype
not specified Benign:5
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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. -
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Catecholaminergic polymorphic ventricular tachycardia 2 Benign:4
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This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -
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Cardiomyopathy Benign:1
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not provided Benign:1
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Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at