chr1-115725557-G-GAA

Position:

• chr1-115725557-G-GAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The ENST00000261448.6(CASQ2):​c.738-5_738-4insTT 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 0.00041 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (16 hom.)
• Consequence: CASQ2 ENST00000261448.6 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00435 (5575/1280466) while in subpopulation AMR AF= 0.0216 (673/31136). AF 95% confidence interval is 0.0203. There are 16 homozygotes in gnomad4_exome. There are 2922 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 16 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASQ2	NM_001232.4	c.738-5_738-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6	c.738-5_738-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_001232.4	ENSP00000261448	P1
CASQ2	ENST00000488931.2	c.*110-5_*110-4insTT		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, NMD_transcript_variant		3		ENSP00000518226

Frequencies

GnomAD3 genomes AF: 0.000412 AC: 47 AN: 113962 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000617

Gnomad AMI AF: 0.00130

Gnomad AMR AF: 0.000485

Gnomad ASJ AF: 0.000334

Gnomad EAS AF: 0.00105

Gnomad SAS AF: 0.000912

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000229

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00435 AC: 5575 AN: 1280466 Hom.: 16 Cov.: 0 AF XY: 0.00458 AC XY: 2922 AN XY: 637704

Gnomad4 AFR exome AF: 0.0141

Gnomad4 AMR exome AF: 0.0216

Gnomad4 ASJ exome AF: 0.00838

Gnomad4 EAS exome AF: 0.00797

Gnomad4 SAS exome AF: 0.00933

Gnomad4 FIN exome AF: 0.00556

Gnomad4 NFE exome AF: 0.00296

Gnomad4 OTH exome AF: 0.00361

GnomAD4 genome AF: 0.000413 AC: 47 AN: 113934 Hom.: 0 Cov.: 0 AF XY: 0.000416 AC XY: 22 AN XY: 52858

Gnomad4 AFR AF: 0.000616

Gnomad4 AMR AF: 0.000485

Gnomad4 ASJ AF: 0.000334

Gnomad4 EAS AF: 0.00105

Gnomad4 SAS AF: 0.000920

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.000229

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;