1-115725557-GAAAAAAAAAAAAAAA-GAAAAAAAAAA
Variant summary
Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate
The NM_001232.4(CASQ2):c.738-9_738-5delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,278,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).
Frequency
Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0024 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
CASQ2
NM_001232.4 splice_region, intron
NM_001232.4 splice_region, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.72
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: AR, AD Classification: DEFINITIVE, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet
- catecholaminergic polymorphic ventricular tachycardia 2Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, 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 -2 ACMG points.
BP6
Variant 1-115725557-GAAAAA-G is Benign according to our data. Variant chr1-115725557-GAAAAA-G is described in ClinVar as Benign. ClinVar VariationId is 928920.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001232.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CASQ2 | NM_001232.4 | MANE Select | c.738-9_738-5delTTTTT | splice_region intron | N/A | NP_001223.2 | O14958-1 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| CASQ2 | ENST00000261448.6 | TSL:1 MANE Select | c.738-9_738-5delTTTTT | splice_region intron | N/A | ENSP00000261448.5 | O14958-1 | ||
| CASQ2 | ENST00000713711.1 | c.879-9_879-5delTTTTT | splice_region intron | N/A | ENSP00000519014.1 | A0AAQ5BGS1 | |||
| CASQ2 | ENST00000874189.1 | c.738-9_738-5delTTTTT | splice_region intron | N/A | ENSP00000544248.1 |
Frequencies
GnomAD3 genomes 0.00 AC: 0AN: 114030Hom.: 0 Cov.: 0
GnomAD3 genomes
AF:
AC:
0
AN:
114030
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: 0.00242 AC: 3095AN: 1278340Hom.: 0 AF XY: 0.00247 AC XY: 1574AN XY: 636780 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
3095
AN:
1278340
Hom.:
AF XY:
AC XY:
1574
AN XY:
636780
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
148
AN:
28034
American (AMR)
AF:
AC:
134
AN:
31482
Ashkenazi Jewish (ASJ)
AF:
AC:
48
AN:
22588
East Asian (EAS)
AF:
AC:
181
AN:
35902
South Asian (SAS)
AF:
AC:
158
AN:
72252
European-Finnish (FIN)
AF:
AC:
155
AN:
36718
Middle Eastern (MID)
AF:
AC:
6
AN:
3640
European-Non Finnish (NFE)
AF:
AC:
2100
AN:
994674
Other (OTH)
AF:
AC:
165
AN:
53050
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.274
Heterozygous variant carriers
0
333
666
1000
1333
1666
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
72
144
216
288
360
<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 0.00 AC: 0AN: 114000Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0AN XY: 52882
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
114000
Hom.:
Cov.:
0
AF XY:
AC XY:
0
AN XY:
52882
African (AFR)
AF:
AC:
0
AN:
30842
American (AMR)
AF:
AC:
0
AN:
10306
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
2992
East Asian (EAS)
AF:
AC:
0
AN:
3814
South Asian (SAS)
AF:
AC:
0
AN:
3260
European-Finnish (FIN)
AF:
AC:
0
AN:
3528
Middle Eastern (MID)
AF:
AC:
0
AN:
224
European-Non Finnish (NFE)
AF:
AC:
0
AN:
56720
Other (OTH)
AF:
AC:
0
AN:
1546
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Benign
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
-
-
3
not specified (3)
Computational 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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