1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAA

Position:

• chr1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAAAAAAAAAAAAA

Variant summary

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

The NM_001232.4(CASQ2):​c.738-5_738-4insTTTTTT 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 0.000035 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (4 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 = 0.000158 (203/1288452) while in subpopulation MID AF= 0.00163 (6/3678). AF 95% confidence interval is 0.00071. There are 4 homozygotes in gnomad4_exome. There are 108 alleles in male gnomad4_exome subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0000351 AC: 4 AN: 113996 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

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: 0.0000353

Gnomad OTH AF: 0.000648

GnomAD4 exome AF: 0.000158 AC: 203 AN: 1288452 Hom.: 4 Cov.: 0 AF XY: 0.000168 AC XY: 108 AN XY: 641788

Gnomad4 AFR exome AF: 0.000423

Gnomad4 AMR exome AF: 0.000911

Gnomad4 ASJ exome AF: 0.000439

Gnomad4 EAS exome AF: 0.000357

Gnomad4 SAS exome AF: 0.000371

Gnomad4 FIN exome AF: 0.0000807

Gnomad4 NFE exome AF: 0.0000968

Gnomad4 OTH exome AF: 0.000112

GnomAD4 genome AF: 0.0000351 AC: 4 AN: 113966 Hom.: 0 Cov.: 0 AF XY: 0.0000567 AC XY: 3 AN XY: 52868

Gnomad4 AFR AF: 0.00

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: 0.0000353

Gnomad4 OTH AF: 0.000647

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;