Genetic Variant NM_001232.4:c.738-21_738-5dupTTTTTTTTTTTTTTTTT (chr1-115725557-G-GAAAAAAAAAAAAAAAAA) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001232.4(CASQ2):c.738-21_738-5dupTTTTTTTTTTTTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0000093 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

CASQ2
NM_001232.4 splice_region, intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.516

Publications

0 publications found

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 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

CASQ2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAdExome4 at 3 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4 link	c.738-21_738-5dupTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 6 of 10	ENST00000261448.6	NP_001223.2	O14958-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448.6 link	c.738-5_738-4insTTTTTTTTTTTTTTTTT		splice_region_variant, intron_variant	Intron 6 of 10	1	NM_001232.4	ENSP00000261448.5		O14958-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

114030

Hom.:

Cov.:

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000931

AC:

AN:

1288848

Hom.:

Cov.:

AF XY:

0.0000156

AC XY:

AN XY:

642018

show subpopulations

African (AFR)

AF:

0.0000705

AC:

AN:

28378

American (AMR)

AF:

0.00

AC:

AN:

31834

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22774

East Asian (EAS)

AF:

0.00

AC:

AN:

36490

South Asian (SAS)

AF:

0.00

AC:

AN:

72760

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37158

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3680

European-Non Finnish (NFE)

AF:

0.00000798

AC:

AN:

1002266

Other (OTH)

AF:

0.0000374

AC:

AN:

53508

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.600

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

114030

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

52882

African (AFR)

AF:

0.00

AC:

AN:

30806

American (AMR)

AF:

0.00

AC:

AN:

10302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2992

East Asian (EAS)

AF:

0.00

AC:

AN:

3824

South Asian (SAS)

AF:

0.00

AC:

AN:

3288

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3528

Middle Eastern (MID)

AF:

0.00

AC:

AN:

246

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

56732

Other (OTH)

AF:

0.00

AC:

AN:

1544

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.52

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over