1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAA
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP6_ModerateBS1
The NM_001232.4(CASQ2):c.738-10_738-5delTTTTTT variant causes a splice region, intron change. The variant allele was found at a frequency of 0.00124 in 1,399,780 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
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CASQ2 | ENST00000261448.6 | c.738-10_738-5delTTTTTT | splice_region_variant, intron_variant | Intron 6 of 10 | 1 | NM_001232.4 | ENSP00000261448.5 | |||
CASQ2 | ENST00000488931.2 | n.*110-10_*110-5delTTTTTT | splice_region_variant, intron_variant | Intron 8 of 12 | 3 | ENSP00000518226.1 |
Frequencies
GnomAD3 genomes AF: 0.000623 AC: 71AN: 114030Hom.: 0 Cov.: 0
GnomAD4 exome AF: 0.00130 AC: 1671AN: 1285780Hom.: 0 AF XY: 0.00124 AC XY: 795AN XY: 640494
GnomAD4 genome AF: 0.000623 AC: 71AN: 114000Hom.: 0 Cov.: 0 AF XY: 0.000586 AC XY: 31AN XY: 52882
ClinVar
Submissions by phenotype
not specified Benign:1
Variant summary: CASQ2 c.738-10_738-5delTTTTTT alters a 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. 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.738-10_738-5delTTTTTT in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at