1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_001232.4(CASQ2):c.738-5_738-4insTTTT variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00046 (10 hom.)
• Consequence: CASQ2 NM_001232.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.516

Genes affected

CASQ2 (HGNC:1513): (calsequestrin 2) The protein encoded by this gene specifies the cardiac muscle family member of the calsequestrin family. Calsequestrin is localized to the sarcoplasmic reticulum in cardiac and slow skeletal muscle cells. The protein is a calcium binding protein that stores calcium for muscle function. Mutations in this gene cause stress-induced polymorphic ventricular tachycardia, also referred to as catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2), a disease characterized by bidirectional ventricular tachycardia that may lead to cardiac arrest. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.000457 (589/1287970) while in subpopulation AMR AF= 0.00164 (52/31744). AF 95% confidence interval is 0.00128. There are 10 homozygotes in gnomad4_exome. There are 308 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ2	NM_001232.4	c.738-5_738-4insTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261448.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ2	ENST00000261448.6	c.738-5_738-4insTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001232.4	P1
CASQ2	ENST00000488931.2	c.*110-5_*110-4insTTTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000342 AC: 39 AN: 113986 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000325

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000291

Gnomad ASJ AF: 0.000668

Gnomad EAS AF: 0.000523

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000457 AC: 589 AN: 1287970 Hom.: 10 Cov.: 0 AF XY: 0.000480 AC XY: 308 AN XY: 641560

Gnomad4 AFR exome AF: 0.000988

Gnomad4 AMR exome AF: 0.00164

Gnomad4 ASJ exome AF: 0.00110

Gnomad4 EAS exome AF: 0.000878

Gnomad4 SAS exome AF: 0.00123

Gnomad4 FIN exome AF: 0.000377

Gnomad4 NFE exome AF: 0.000327

Gnomad4 OTH exome AF: 0.000355

GnomAD4 genome AF: 0.000342 AC: 39 AN: 113956 Hom.: 0 Cov.: 0 AF XY: 0.000303 AC XY: 16 AN XY: 52862

Gnomad4 AFR AF: 0.0000324

Gnomad4 AMR AF: 0.000291

Gnomad4 ASJ AF: 0.000668

Gnomad4 EAS AF: 0.000524

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56889721; hg19: chr1-116268178;