1-115700223-A-AT

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting

The NM_001232.4(CASQ2):c.*1017_*1018insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0019 (1 hom., cov: 0)
  • Exomes 𝑓: 0.0025 (0 hom.)
• Consequence: CASQ2 NM_001232.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.400

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 Likely_benign. Variant got -1 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00186 (276/148044) while in subpopulation AFR AF= 0.00274 (111/40442). AF 95% confidence interval is 0.00233. There are 1 homozygotes in gnomad4. There are 138 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASQ2	NM_001232.4	c.*1017_*1018insA		3_prime_UTR_variant	11/11	ENST00000261448.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ2	ENST00000261448.6	c.*1017_*1018insA		3_prime_UTR_variant	11/11	1	NM_001232.4	P1
CASQ2	ENST00000488931.2	c.*1589_*1590insA		3_prime_UTR_variant, NMD_transcript_variant	13/13	3

Frequencies

GnomAD3 genomes AF: 0.00185 AC: 273 AN: 147962 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.00268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000735

Gnomad ASJ AF: 0.00935

Gnomad EAS AF: 0.000989

Gnomad SAS AF: 0.00149

Gnomad FIN AF: 0.00167

Gnomad MID AF: 0.00658

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.00196

GnomAD4 exome AF: 0.00251 AC: 1 AN: 398 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 240

Gnomad4 FIN exome AF: 0.00255

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00186 AC: 276 AN: 148044 Hom.: 1 Cov.: 0 AF XY: 0.00191 AC XY: 138 AN XY: 72098

Gnomad4 AFR AF: 0.00274

Gnomad4 AMR AF: 0.000735

Gnomad4 ASJ AF: 0.00935

Gnomad4 EAS AF: 0.000992

Gnomad4 SAS AF: 0.00149

Gnomad4 FIN AF: 0.00167

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.00194

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia Uncertain:1

Uncertain significance, 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: rs11347859; hg19: chr1-116242844;