1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAA

Position:

• chr1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAA

Variant summary

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

The NM_001232.4(CASQ2):​c.738-5_738-4insTTT 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 0.000070 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00075 (6 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00075 (966/1287204) while in subpopulation AMR AF= 0.00521 (165/31648). AF 95% confidence interval is 0.00456. There are 6 homozygotes in gnomad4_exome. There are 523 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 6 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000702 AC: 8 AN: 114022 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000130

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000529

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000750 AC: 966 AN: 1287204 Hom.: 6 Cov.: 0 AF XY: 0.000816 AC XY: 523 AN XY: 641170

Gnomad4 AFR exome AF: 0.00162

Gnomad4 AMR exome AF: 0.00521

Gnomad4 ASJ exome AF: 0.00211

Gnomad4 EAS exome AF: 0.00148

Gnomad4 SAS exome AF: 0.00171

Gnomad4 FIN exome AF: 0.00102

Gnomad4 NFE exome AF: 0.000442

Gnomad4 OTH exome AF: 0.000861

GnomAD4 genome AF: 0.0000702 AC: 8 AN: 113992 Hom.: 0 Cov.: 0 AF XY: 0.0000567 AC XY: 3 AN XY: 52876

Gnomad4 AFR AF: 0.000130

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.0000529

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;