rs1140238

Variant names:

• chr1-115700609-C-G
• rs1140238
• NM_001232.4:c.*632G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-115700609-C-G
• chr1-115700609-C-A
• chr1-115700609-C-T

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.*632G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.65 in 170,186 control chromosomes in the GnomAD database, including 36,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.66 (33469 hom., cov: 32)
  • Exomes 𝑓: 0.60 (3438 hom.)
• Consequence: CASQ2 NM_001232.4 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.401
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 1-115700609-C-G is Benign according to our data. Variant chr1-115700609-C-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 292120.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.775 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.*632G>C		3_prime_UTR	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.*632G>C		3_prime_UTR	Exon 11 of 11	ENSP00000261448.5	O14958-1
	CASQ2	ENST00000713711.1		c.*632G>C		3_prime_UTR	Exon 12 of 12	ENSP00000519014.1	A0AAQ5BGS1
	CASQ2	ENST00000874189.1		c.*632G>C		3_prime_UTR	Exon 10 of 10	ENSP00000544248.1

Frequencies

GnomAD3 genomes AF: 0.656 AC: 99678 AN: 151890 Hom.: 33419 Cov.: 32

Gnomad AFR AF: 0.782

Gnomad AMI AF: 0.643

Gnomad AMR AF: 0.685

Gnomad ASJ AF: 0.552

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.631

Gnomad MID AF: 0.646

Gnomad NFE AF: 0.579

Gnomad OTH AF: 0.661

GnomAD4 exome AF: 0.598 AC: 10877 AN: 18178 Hom.: 3438 Cov.: 0 AF XY: 0.601 AC XY: 5564 AN XY: 9260

African (AFR) AF: 0.783 AC: 296 AN: 378

American (AMR) AF: 0.726 AC: 2072 AN: 2854

Ashkenazi Jewish (ASJ) AF: 0.541 AC: 226 AN: 418

East Asian (EAS) AF: 0.665 AC: 704 AN: 1058

South Asian (SAS) AF: 0.607 AC: 905 AN: 1490

European-Finnish (FIN) AF: 0.559 AC: 266 AN: 476

Middle Eastern (MID) AF: 0.719 AC: 46 AN: 64

European-Non Finnish (NFE) AF: 0.553 AC: 5860 AN: 10596

Other (OTH) AF: 0.595 AC: 502 AN: 844

GnomAD4 genome AF: 0.656 AC: 99786 AN: 152008 Hom.: 33469 Cov.: 32 AF XY: 0.661 AC XY: 49090 AN XY: 74312

African (AFR) AF: 0.782 AC: 32440 AN: 41460

American (AMR) AF: 0.686 AC: 10479 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.552 AC: 1913 AN: 3468

East Asian (EAS) AF: 0.708 AC: 3656 AN: 5162

South Asian (SAS) AF: 0.646 AC: 3108 AN: 4808

European-Finnish (FIN) AF: 0.631 AC: 6652 AN: 10542

Middle Eastern (MID) AF: 0.650 AC: 191 AN: 294

European-Non Finnish (NFE) AF: 0.579 AC: 39372 AN: 67974

Other (OTH) AF: 0.659 AC: 1391 AN: 2112

Alfa AF: 0.608 Hom.: 3522

Bravo AF: 0.668

Asia WGS AF: 0.691 AC: 2407 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Catecholaminergic polymorphic ventricular tachycardia (1)
-	-	1	Catecholaminergic polymorphic ventricular tachycardia 2 (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	-0.93
CADD	Benign	0.28
DANN	Benign	0.42
PhyloP100		-0.40
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: rs1140238; hg19: chr1-116243230;