ENST00000850611.1:c.-632+28394A>G

Variant names:

• chr1-115805806-T-C
• rs4272626
• ENST00000850611.1:c.-632+28394A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000850611.1(CASQ2):​c.-632+28394A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 151,854 control chromosomes in the GnomAD database, including 27,335 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.60 (27335 hom., cov: 30)
• Consequence: CASQ2 ENST00000850611.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.25
• Publications: 3 publications found

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]

CASQ2 Gene-Disease associations (from GenCC):

• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD, AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• catecholaminergic polymorphic ventricular tachycardia 2

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
• hypertrophic cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.628 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000850611.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ2	ENST00000850611.1		c.-632+28394A>G		intron	N/A	ENSP00000520899.1

Frequencies

GnomAD3 genomes AF: 0.599 AC: 90843 AN: 151736 Hom.: 27317 Cov.: 30

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.617

Gnomad ASJ AF: 0.653

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.514

Gnomad FIN AF: 0.617

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.633

Gnomad OTH AF: 0.580

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.599 AC: 90906 AN: 151854 Hom.: 27335 Cov.: 30 AF XY: 0.597 AC XY: 44319 AN XY: 74226

African (AFR) AF: 0.546 AC: 22595 AN: 41372

American (AMR) AF: 0.617 AC: 9417 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.653 AC: 2265 AN: 3466

East Asian (EAS) AF: 0.510 AC: 2618 AN: 5134

South Asian (SAS) AF: 0.512 AC: 2463 AN: 4814

European-Finnish (FIN) AF: 0.617 AC: 6506 AN: 10550

Middle Eastern (MID) AF: 0.517 AC: 151 AN: 292

European-Non Finnish (NFE) AF: 0.633 AC: 42980 AN: 67940

Other (OTH) AF: 0.577 AC: 1218 AN: 2110

Alfa AF: 0.598 Hom.: 5634

Bravo AF: 0.600

Asia WGS AF: 0.525 AC: 1824 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	22
DANN	Benign	0.79
PhyloP100		1.2

Splicing

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

Other links and lift over

dbSNP: rs4272626; hg19: chr1-116348427;