1-115725557-GAAAAAAAAAAAAAAA-GAAAAAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001232.4(CASQ2):c.738-13_738-5del variant causes a splice region, splice polypyrimidine tract, intron change. The variant allele was found at a frequency of 0.000121 in 1,402,772 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000088 (1 hom., cov: 0)
  • Exomes 𝑓: 0.00012 (0 hom.)
• Consequence: CASQ2 NM_001232.4 splice_region, splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.12

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4_exome allele frequency = 0.000124 (160/1288742) while in subpopulation AFR AF= 0.00074 (21/28362). AF 95% confidence interval is 0.000496. There are 0 homozygotes in gnomad4_exome. There are 77 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ2	NM_001232.4	c.738-13_738-5del		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.738-13_738-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001232.4	P1
CASQ2	ENST00000488931.2	c.*110-13_*110-5del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0000877 AC: 10 AN: 114030 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0000649

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000194

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00122

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000353

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000124 AC: 160 AN: 1288742 Hom.: 0 AF XY: 0.000120 AC XY: 77 AN XY: 641972

Gnomad4 AFR exome AF: 0.000740

Gnomad4 AMR exome AF: 0.0000943

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000632

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000838

Gnomad4 OTH exome AF: 0.0000934

GnomAD4 genome AF: 0.0000877 AC: 10 AN: 114030 Hom.: 1 Cov.: 0 AF XY: 0.0000946 AC XY: 5 AN XY: 52882

Gnomad4 AFR AF: 0.0000649

Gnomad4 AMR AF: 0.000194

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00122

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000353

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;