rs397516640
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_001232.4(CASQ2):āc.1148A>Gā(p.Asp383Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000077 in 1,533,200 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D383E) has been classified as Uncertain significance.
Frequency
Consequence
NM_001232.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CASQ2 | NM_001232.4 | c.1148A>G | p.Asp383Gly | missense_variant | 11/11 | ENST00000261448.6 | NP_001223.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.1148A>G | p.Asp383Gly | missense_variant | 11/11 | 1 | NM_001232.4 | ENSP00000261448.5 | ||
CASQ2 | ENST00000488931.2 | n.*520A>G | non_coding_transcript_exon_variant | 13/13 | 3 | ENSP00000518226.1 | ||||
CASQ2 | ENST00000488931.2 | n.*520A>G | 3_prime_UTR_variant | 13/13 | 3 | ENSP00000518226.1 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152060Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000919 AC: 23AN: 250316Hom.: 0 AF XY: 0.0000961 AC XY: 13AN XY: 135268
GnomAD4 exome AF: 0.0000782 AC: 108AN: 1381140Hom.: 0 Cov.: 26 AF XY: 0.0000712 AC XY: 49AN XY: 688440
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152060Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74274
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 15, 2012 | The Asp383Gly variant in CASQ2 has not been reported in the literature nor previ ously identified by our laboratory. This variant has not been identified in 2 ve ry large and broad populations (European and African American) sequenced by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). This low freq uency is consistent with a disease causing role, but insufficient to establish t his with confidence. Computational analyses (biochemical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully a ssess the clinical significance of this variant. - |
Catecholaminergic polymorphic ventricular tachycardia 2 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Oct 18, 2022 | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 383 of the CASQ2 protein (p.Asp383Gly). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with Brugada Syndrome (PMID: 26230511). ClinVar contains an entry for this variant (Variation ID: 44156). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 08, 2024 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at