Variant 1-115701098-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001232.4(CASQ2):c.*143G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00235 in 1,282,318 control chromosomes in the GnomAD database, including 88 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0029 ( 13 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 75 hom. )

Consequence

CASQ2
NM_001232.4 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.558

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-115701098-C-T is Benign according to our data. Variant chr1-115701098-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 368821.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.07 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASQ2	NM_001232.4 linkuse as main transcript	c.*143G>A		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	ENST00000261448.6 linkuse as main transcript	c.*143G>A		3_prime_UTR_variant	11/11	1	NM_001232.4	ENSP00000261448	P1	O14958-1
CASQ2	ENST00000488931.2 linkuse as main transcript	c.*715G>A		3_prime_UTR_variant, NMD_transcript_variant	13/13	3		ENSP00000518226

Frequencies

GnomAD3 genomes

AF:

0.00287

AC:

436

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000852

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.0762

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00287

GnomAD4 exome

AF:

0.00228

AC:

2578

AN:

1130144

Hom.:

Cov.:

AF XY:

0.00220

AC XY:

1268

AN XY:

577362

show subpopulations

Gnomad4 AFR exome

AF:

0.0000372

Gnomad4 AMR exome

AF:

0.000113

Gnomad4 ASJ exome

AF:

0.000377

Gnomad4 EAS exome

AF:

0.0594

Gnomad4 SAS exome

AF:

0.000926

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000699

Gnomad4 OTH exome

AF:

0.00340

GnomAD4 genome

AF:

0.00286

AC:

435

AN:

152174

Hom.:

Cov.:

AF XY:

0.00297

AC XY:

221

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.0000964

Gnomad4 AMR

AF:

0.000851

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.0762

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000418

Hom.:

Bravo

AF:

0.00301

Asia WGS

AF:

0.0190

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Apr 27, 2017

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. -

Caudal regression sequence

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.4

DANN

Benign

0.53

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over