1-115700223-ATTT-ATT

Variant names:

• chr1-115700223-AT-A
• rs11347859
• NM_001232.4:c.*1017delA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001232.4(CASQ2):​c.*1017delA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.31 (6951 hom., cov: 0)
  • Exomes 𝑓: 0.45 (12 hom.)
• Consequence: CASQ2 NM_001232.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:3
• Conservation: PhyloP100: -0.400
• Publications: 0 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 -10 ACMG points.

• BP6: Variant 1-115700223-AT-A is Benign according to our data. Variant chr1-115700223-AT-A is described in ClinVar as Likely_benign. ClinVar VariationId is 292118.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 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.*1017delA		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.*1017delA		3_prime_UTR	Exon 11 of 11	ENSP00000261448.5	O14958-1
	CASQ2	ENST00000713711.1		c.*1017delA		3_prime_UTR	Exon 12 of 12	ENSP00000519014.1	A0AAQ5BGS1
	CASQ2	ENST00000874189.1		c.*1017delA		3_prime_UTR	Exon 10 of 10	ENSP00000544248.1

Frequencies

GnomAD3 genomes AF: 0.308 AC: 45503 AN: 147718 Hom.: 6935 Cov.: 0

Gnomad AFR AF: 0.287

Gnomad AMI AF: 0.394

Gnomad AMR AF: 0.384

Gnomad ASJ AF: 0.284

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.389

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.332

Gnomad NFE AF: 0.301

Gnomad OTH AF: 0.330

GnomAD4 exome AF: 0.454 AC: 159 AN: 350 Hom.: 12 Cov.: 0 AF XY: 0.471 AC XY: 99 AN XY: 210

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.451 AC: 155 AN: 344

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 1 AN: 2

Other (OTH) AF: 0.750 AC: 3 AN: 4

GnomAD4 genome AF: 0.308 AC: 45565 AN: 147796 Hom.: 6951 Cov.: 0 AF XY: 0.313 AC XY: 22544 AN XY: 71942

African (AFR) AF: 0.287 AC: 11594 AN: 40388

American (AMR) AF: 0.385 AC: 5746 AN: 14942

Ashkenazi Jewish (ASJ) AF: 0.284 AC: 971 AN: 3416

East Asian (EAS) AF: 0.201 AC: 1014 AN: 5040

South Asian (SAS) AF: 0.389 AC: 1828 AN: 4694

European-Finnish (FIN) AF: 0.340 AC: 3248 AN: 9560

Middle Eastern (MID) AF: 0.330 AC: 93 AN: 282

European-Non Finnish (NFE) AF: 0.301 AC: 20035 AN: 66516

Other (OTH) AF: 0.331 AC: 679 AN: 2052

Alfa AF: 0.128 Hom.: 193

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Catecholaminergic polymorphic ventricular tachycardia (1)
-	-	1	Caudal regression sequence (1)
-	-	1	Neural tube defect (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
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: rs11347859; hg19: chr1-116242844; COSMIC: COSV54769911; COSMIC: COSV54769911;