rs7413162

Variant names:

• chr1-115701256-G-A
• rs7413162
• NM_001232.4:c.1185C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-115701256-G-A
• chr1-115701256-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001232.4(CASQ2):​c.1185C>T​(p.Asp395Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.37 in 1,592,320 control chromosomes in the GnomAD database, including 108,018 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.40 (12002 hom., cov: 31)
  • Exomes 𝑓: 0.37 (96016 hom.)
• Consequence: CASQ2 NM_001232.4 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:17
• Conservation: PhyloP100: -1.80
• Publications: 15 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: AR, AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• catecholaminergic polymorphic ventricular tachycardia 2

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 1-115701256-G-A is Benign according to our data. Variant chr1-115701256-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 44157.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.8 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.447 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001232.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ2	NM_001232.4	MANE Select	c.1185C>T	p.Asp395Asp	synonymous	Exon 11 of 11	NP_001223.2	O14958-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASQ2	ENST00000261448.6	TSL:1 MANE Select	c.1185C>T	p.Asp395Asp	synonymous	Exon 11 of 11	ENSP00000261448.5	O14958-1
	CASQ2	ENST00000713711.1		c.1326C>T	p.Asp442Asp	synonymous	Exon 12 of 12	ENSP00000519014.1	A0AAQ5BGS1
	CASQ2	ENST00000874189.1		c.1110C>T	p.Asp370Asp	synonymous	Exon 10 of 10	ENSP00000544248.1

Frequencies

GnomAD3 genomes AF: 0.397 AC: 59905 AN: 150950 Hom.: 11979 Cov.: 31

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.435

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.359

Gnomad OTH AF: 0.420

GnomAD2 exomes AF: 0.381 AC: 95474 AN: 250554 AF XY: 0.380

Gnomad AFR exome AF: 0.451

Gnomad AMR exome AF: 0.440

Gnomad ASJ exome AF: 0.406

Gnomad EAS exome AF: 0.290

Gnomad FIN exome AF: 0.394

Gnomad NFE exome AF: 0.355

Gnomad OTH exome AF: 0.403

GnomAD4 exome AF: 0.367 AC: 529264 AN: 1441250 Hom.: 96016 Cov.: 30 AF XY: 0.368 AC XY: 264296 AN XY: 717728

African (AFR) AF: 0.455 AC: 15131 AN: 33270

American (AMR) AF: 0.441 AC: 19672 AN: 44592

Ashkenazi Jewish (ASJ) AF: 0.400 AC: 10439 AN: 26086

East Asian (EAS) AF: 0.364 AC: 14430 AN: 39660

South Asian (SAS) AF: 0.405 AC: 34795 AN: 85918

European-Finnish (FIN) AF: 0.397 AC: 21000 AN: 52934

Middle Eastern (MID) AF: 0.435 AC: 2495 AN: 5734

European-Non Finnish (NFE) AF: 0.356 AC: 388757 AN: 1093308

Other (OTH) AF: 0.377 AC: 22545 AN: 59748

GnomAD4 genome AF: 0.397 AC: 59982 AN: 151070 Hom.: 12002 Cov.: 31 AF XY: 0.401 AC XY: 29642 AN XY: 73838

African (AFR) AF: 0.452 AC: 18688 AN: 41304

American (AMR) AF: 0.432 AC: 6573 AN: 15216

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1356 AN: 3470

East Asian (EAS) AF: 0.298 AC: 1540 AN: 5160

South Asian (SAS) AF: 0.419 AC: 2008 AN: 4794

European-Finnish (FIN) AF: 0.403 AC: 4207 AN: 10450

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.359 AC: 24216 AN: 67374

Other (OTH) AF: 0.418 AC: 878 AN: 2100

Alfa AF: 0.381 Hom.: 16877

Bravo AF: 0.398

Asia WGS AF: 0.400 AC: 1391 AN: 3478

EpiCase AF: 0.366

EpiControl AF: 0.376

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	6	not specified (6)
-	-	4	Catecholaminergic polymorphic ventricular tachycardia 2 (4)
-	-	2	Catecholaminergic polymorphic ventricular tachycardia (2)
-	-	1	Cardiovascular phenotype (1)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 1 (1)
-	-	1	Caudal regression sequence (1)
-	-	1	Neural tube defect (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.13
DANN	Benign	0.57
PhyloP100		-1.8
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: rs7413162; hg19: chr1-116243877; COSMIC: COSV54770824; COSMIC: COSV54770824;