chr1-115706482-A-C

Variant names:

• chr1-115706482-A-C
• rs7536370
• NM_001232.4:c.839-1190T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001232.4(CASQ2):​c.839-1190T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 151,912 control chromosomes in the GnomAD database, including 13,289 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 0.40 (13289 hom., cov: 32)
• Consequence: CASQ2 NM_001232.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0370
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.581 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4	c.839-1190T>G		intron_variant	Intron 8 of 10	ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6	c.839-1190T>G		intron_variant	Intron 8 of 10	1	NM_001232.4	ENSP00000261448.5

Frequencies

GnomAD3 genomes AF: 0.395 AC: 60020 AN: 151794 Hom.: 13267 Cov.: 32

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.400

Gnomad AMR AF: 0.338

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.314

Gnomad MID AF: 0.367

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.376

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

GnomAD4 genome AF: 0.396 AC: 60088 AN: 151912 Hom.: 13289 Cov.: 32 AF XY: 0.394 AC XY: 29253 AN XY: 74234

African (AFR) AF: 0.587 AC: 24304 AN: 41370

American (AMR) AF: 0.338 AC: 5166 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.290 AC: 1005 AN: 3464

East Asian (EAS) AF: 0.509 AC: 2627 AN: 5160

South Asian (SAS) AF: 0.291 AC: 1396 AN: 4798

European-Finnish (FIN) AF: 0.314 AC: 3318 AN: 10560

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 21008 AN: 67954

Other (OTH) AF: 0.373 AC: 788 AN: 2114

Alfa AF: 0.354 Hom.: 1385

Bravo AF: 0.409

Asia WGS AF: 0.382 AC: 1331 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.4
DANN	Benign	0.50
PhyloP100		-0.037
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7536370; hg19: chr1-116249103;