rs3811003

Variant names:

• chr1-115705169-G-A
• rs3811003
• NM_001232.4:c.939+23C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-115705169-G-A
• chr1-115705169-G-C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001232.4(CASQ2):​c.939+23C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.332 in 1,440,028 control chromosomes in the GnomAD database, including 83,796 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (12731 hom., cov: 33)
  • Exomes 𝑓: 0.33 (71065 hom.)
• Consequence: CASQ2 NM_001232.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.198

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 1-115705169-G-A is Benign according to our data. Variant chr1-115705169-G-A is described in ClinVar as [Benign]. Clinvar id is 257653.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-115705169-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4	c.939+23C>T		intron_variant	Intron 9 of 10	ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6	c.939+23C>T		intron_variant	Intron 9 of 10	1	NM_001232.4	ENSP00000261448.5
CASQ2	ENST00000488931.2	n.*311+23C>T		intron_variant	Intron 11 of 12	3		ENSP00000518226.1

Frequencies

GnomAD3 genomes AF: 0.389 AC: 59140 AN: 152026 Hom.: 12719 Cov.: 33

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.401

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.290

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.291

Gnomad FIN AF: 0.316

Gnomad MID AF: 0.369

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.373

GnomAD2 exomes AF: 0.346 AC: 86909 AN: 251060 AF XY: 0.338

Gnomad AFR exome AF: 0.569

Gnomad AMR exome AF: 0.366

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.520

Gnomad FIN exome AF: 0.298

Gnomad NFE exome AF: 0.311

Gnomad OTH exome AF: 0.327

GnomAD4 exome AF: 0.326 AC: 419445 AN: 1287882 Hom.: 71065 Cov.: 19 AF XY: 0.323 AC XY: 210046 AN XY: 650278

Gnomad4 AFR exome AF: 0.565 AC: 16994 AN: 30080

Gnomad4 AMR exome AF: 0.364 AC: 16196 AN: 44516

Gnomad4 ASJ exome AF: 0.276 AC: 6914 AN: 25072

Gnomad4 EAS exome AF: 0.479 AC: 18614 AN: 38868

Gnomad4 SAS exome AF: 0.293 AC: 24276 AN: 82944

Gnomad4 FIN exome AF: 0.295 AC: 15740 AN: 53360

Gnomad4 NFE exome AF: 0.315 AC: 300031 AN: 953072

Gnomad4 Remaining exome AF: 0.343 AC: 18715 AN: 54640

GnomAD4 genome AF: 0.389 AC: 59194 AN: 152146 Hom.: 12731 Cov.: 33 AF XY: 0.388 AC XY: 28861 AN XY: 74380

Gnomad4 AFR AF: 0.564 AC: 0.563681 AN: 0.563681

Gnomad4 AMR AF: 0.336 AC: 0.335971 AN: 0.335971

Gnomad4 ASJ AF: 0.290 AC: 0.290081 AN: 0.290081

Gnomad4 EAS AF: 0.510 AC: 0.509694 AN: 0.509694

Gnomad4 SAS AF: 0.292 AC: 0.291632 AN: 0.291632

Gnomad4 FIN AF: 0.316 AC: 0.315899 AN: 0.315899

Gnomad4 NFE AF: 0.309 AC: 0.309158 AN: 0.309158

Gnomad4 OTH AF: 0.370 AC: 0.369915 AN: 0.369915

Alfa AF: 0.337 Hom.: 25112

Bravo AF: 0.401

Asia WGS AF: 0.381 AC: 1328 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 26, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Catecholaminergic polymorphic ventricular tachycardia 2 Benign:1

Apr 11, 2023

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3811003; hg19: chr1-116247790; COSMIC: COSV54768530;