chr1-115725557-G-GAAAAAA
Variant summary
Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2
The NM_001232.4(CASQ2):c.738-10_738-5dupTTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000035 ( 0 hom., cov: 0)
Exomes 𝑓: 0.00016 ( 4 hom. )
Consequence
CASQ2
NM_001232.4 splice_region, intron
NM_001232.4 splice_region, intron
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.516
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 tachycardiaInheritance: AD, AR Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: Orphanet, ClinGen
- catecholaminergic polymorphic ventricular tachycardia 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Genomics England PanelApp
- hypertrophic cardiomyopathyInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
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 4 AR,AD gene
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000351 AC: 4AN: 113996Hom.: 0 Cov.: 0 show subpopulations
GnomAD3 genomes
AF:
AC:
4
AN:
113996
Hom.:
Cov.:
0
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.000158 AC: 203AN: 1288452Hom.: 4 Cov.: 0 AF XY: 0.000168 AC XY: 108AN XY: 641788 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
203
AN:
1288452
Hom.:
Cov.:
0
AF XY:
AC XY:
108
AN XY:
641788
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
12
AN:
28368
American (AMR)
AF:
AC:
29
AN:
31824
Ashkenazi Jewish (ASJ)
AF:
AC:
10
AN:
22766
East Asian (EAS)
AF:
AC:
13
AN:
36464
South Asian (SAS)
AF:
AC:
27
AN:
72688
European-Finnish (FIN)
AF:
AC:
3
AN:
37152
Middle Eastern (MID)
AF:
AC:
6
AN:
3678
European-Non Finnish (NFE)
AF:
AC:
97
AN:
1002038
Other (OTH)
AF:
AC:
6
AN:
53474
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.330
Heterozygous variant carriers
0
19
38
57
76
95
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<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 AF: 0.0000351 AC: 4AN: 113966Hom.: 0 Cov.: 0 AF XY: 0.0000567 AC XY: 3AN XY: 52868 show subpopulations ⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
GnomAD4 genome
AF:
AC:
4
AN:
113966
Hom.:
Cov.:
0
AF XY:
AC XY:
3
AN XY:
52868
show subpopulations
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
30836
American (AMR)
AF:
AC:
0
AN:
10304
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2990
East Asian (EAS)
AF:
AC:
0
AN:
3812
South Asian (SAS)
AF:
AC:
0
AN:
3260
European-Finnish (FIN)
AF:
AC:
1
AN:
3528
Middle Eastern (MID)
AF:
AC:
0
AN:
224
European-Non Finnish (NFE)
AF:
AC:
2
AN:
56698
Other (OTH)
AF:
AC:
1
AN:
1546
⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.054799), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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