1-115706482-A-C

Position:

• chr1-115706482-A-C

Variant summary

Our verdict is Benign. Variant got -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

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 -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/exons	MANE	UniProt
CASQ2	NM_001232.4	c.839-1190T>G		intron_variant		ENST00000261448.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASQ2	ENST00000261448.6	c.839-1190T>G		intron_variant		1	NM_001232.4	P1
CASQ2	ENST00000488931.2	c.*211-1190T>G		intron_variant, NMD_transcript_variant		3

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

Gnomad4 AFR AF: 0.587

Gnomad4 AMR AF: 0.338

Gnomad4 ASJ AF: 0.290

Gnomad4 EAS AF: 0.509

Gnomad4 SAS AF: 0.291

Gnomad4 FIN AF: 0.314

Gnomad4 NFE AF: 0.309

Gnomad4 OTH AF: 0.373

Alfa AF: 0.345 Hom.: 1254

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

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: rs7536370; hg19: chr1-116249103;