1-115700116-CAT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001232.4(CASQ2):c.*1123_*1124del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 152,464 control chromosomes in the GnomAD database, including 4,297 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.24 (4286 hom., cov: 25)
  • Exomes 𝑓: 0.22 (11 hom.)
• Consequence: CASQ2 NM_001232.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.363

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 -10 ACMG points.

• BP6: Variant 1-115700116-CAT-C is Benign according to our data. Variant chr1-115700116-CAT-C is described in ClinVar as [Likely_benign]. Clinvar id is 292115.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.278 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ2	NM_001232.4	c.*1123_*1124del		3_prime_UTR_variant	11/11	ENST00000261448.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ2	ENST00000261448.6	c.*1123_*1124del		3_prime_UTR_variant	11/11	1	NM_001232.4	P1
CASQ2	ENST00000488931.2	c.*1695_*1696del		3_prime_UTR_variant, NMD_transcript_variant	13/13	3

Frequencies

GnomAD3 genomes AF: 0.237 AC: 35966 AN: 151918 Hom.: 4279 Cov.: 25

Gnomad AFR AF: 0.220

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.276

Gnomad ASJ AF: 0.216

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.290

Gnomad FIN AF: 0.232

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.222 AC: 95 AN: 428 Hom.: 11 AF XY: 0.207 AC XY: 53 AN XY: 256

Gnomad4 FIN exome AF: 0.220

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.237 AC: 36009 AN: 152036 Hom.: 4286 Cov.: 25 AF XY: 0.239 AC XY: 17742 AN XY: 74306

Gnomad4 AFR AF: 0.221

Gnomad4 AMR AF: 0.276

Gnomad4 ASJ AF: 0.216

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.232

Gnomad4 NFE AF: 0.239

Gnomad4 OTH AF: 0.255

Alfa AF: 0.243 Hom.: 520

Bravo AF: 0.239

Asia WGS AF: 0.258 AC: 895 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Caudal regression sequence Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neural tube defect Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56839330; hg19: chr1-116242737; COSMIC: COSV54772750; COSMIC: COSV54772750;