1-115725557-GAAAAAAAAAAAAAAA-G

Variant names:

• chr1-115725557-GAAAAAAAAAAAAAAA-G
• rs56889721
• NM_001232.4:c.738-19_738-5delTTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_001232.4(CASQ2):​c.738-19_738-5delTTTTTTTTTTTTTTT variant causes a splice region, intron change. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: CASQ2 NM_001232.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 6.12
• Publications: 3 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: AD, AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
• catecholaminergic polymorphic ventricular tachycardia 2

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 1-115725557-GAAAAAAAAAAAAAAA-G is Benign according to our data. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-115725557-GAAAAAAAAAAAAAAA-G is described in CliVar as Likely_benign. Clinvar id is 2912893.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4	c.738-19_738-5delTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 6 of 10	ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6	c.738-19_738-5delTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 6 of 10	1	NM_001232.4	ENSP00000261448.5

Frequencies

GnomAD3 genomes Cov.: 0

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 284

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1

Mar 09, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs56889721; hg19: chr1-116268178;