1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAA

Position:

• chr1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAA

Variant summary

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

The NM_001232.4(CASQ2):​c.738-5_738-4insTTTTT 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 0.00017 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00024 (12 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 mid. gnomad4_exome allele frequency = 0.000243 (313/1288520) while in subpopulation MID AF= 0.00136 (5/3678). AF 95% confidence interval is 0.000812. There are 12 homozygotes in gnomad4_exome. There are 174 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.000167 AC: 19 AN: 114024 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000357

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000971

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000523

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000567

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000529

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000243 AC: 313 AN: 1288520 Hom.: 12 Cov.: 0 AF XY: 0.000271 AC XY: 174 AN XY: 641834

Gnomad4 AFR exome AF: 0.000352

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.000659

Gnomad4 EAS exome AF: 0.000521

Gnomad4 SAS exome AF: 0.000646

Gnomad4 FIN exome AF: 0.000135

Gnomad4 NFE exome AF: 0.000162

Gnomad4 OTH exome AF: 0.000280

GnomAD4 genome AF: 0.000167 AC: 19 AN: 113994 Hom.: 0 Cov.: 0 AF XY: 0.000170 AC XY: 9 AN XY: 52880

Gnomad4 AFR AF: 0.000357

Gnomad4 AMR AF: 0.0000970

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000524

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000567

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;