1-115701291-TATCATC-TATC
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001232.4(CASQ2):c.1147_1149delGAT(p.Asp383del) variant causes a conservative inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00035 in 1,590,878 control chromosomes in the GnomAD database, including 3 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001232.4 conservative_inframe_deletion
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.1147_1149delGAT | p.Asp383del | conservative_inframe_deletion | Exon 11 of 11 | 1 | NM_001232.4 | ENSP00000261448.5 | ||
CASQ2 | ENST00000488931.2 | n.*519_*521delGAT | non_coding_transcript_exon_variant | Exon 13 of 13 | 3 | ENSP00000518226.1 | ||||
CASQ2 | ENST00000488931.2 | n.*519_*521delGAT | 3_prime_UTR_variant | Exon 13 of 13 | 3 | ENSP00000518226.1 |
Frequencies
GnomAD3 genomes AF: 0.000243 AC: 37AN: 152084Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000284 AC: 71AN: 250136Hom.: 0 AF XY: 0.000259 AC XY: 35AN XY: 135164
GnomAD4 exome AF: 0.000359 AC: 516AN: 1438676Hom.: 1 AF XY: 0.000367 AC XY: 263AN XY: 717050
GnomAD4 genome AF: 0.000269 AC: 41AN: 152202Hom.: 2 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74406
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
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Thep.Asp378[5] variant in CASQ2 is classified as likely benign because it has been identified in 0.05% (16/30482) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant is a deletion of one amino acid at position 383 which occurs within a repetitive region of 6 amino acids and is not predicted to alter the protein reading-frame. ACMG/AMP Criteria applied: BS1, BP3. -
Catecholaminergic polymorphic ventricular tachycardia Uncertain:1
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Cardiomyopathy Uncertain:1
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Catecholaminergic polymorphic ventricular tachycardia 2 Uncertain:1
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Catecholaminergic polymorphic ventricular tachycardia 1 Uncertain:1
This variant, c.1147_1149del, results in the deletion of 1 amino acid(s) of the CASQ2 protein (p.Asp383del), but otherwise preserves the integrity of the reading frame. 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 variant has not been reported in the literature in individuals affected with CASQ2-related conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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
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