1-115700223-AT-A

Position:

• chr1-115700223-AT-A

Variant summary

Our verdict is Benign. Variant got -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

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASQ2	NM_001232.4	c.*1017delA		3_prime_UTR_variant	11/11	ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448	c.*1017delA		3_prime_UTR_variant	11/11	1	NM_001232.4	ENSP00000261448.5
CASQ2	ENST00000488931.2	n.*1589delA		non_coding_transcript_exon_variant	13/13	3		ENSP00000518226.1
CASQ2	ENST00000488931.2	n.*1589delA		3_prime_UTR_variant	13/13	3		ENSP00000518226.1

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

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.500

Gnomad4 OTH exome AF: 0.750

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

Gnomad4 AFR AF: 0.287

Gnomad4 AMR AF: 0.385

Gnomad4 ASJ AF: 0.284

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.389

Gnomad4 FIN AF: 0.340

Gnomad4 NFE AF: 0.301

Gnomad4 OTH AF: 0.331

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Caudal regression sequence Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neural tube defect Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

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: rs11347859; hg19: chr1-116242844;