dbSNP rs3181166: CASP2:c.74+1276T>G (chr7-143289805-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_032982.4(CASP2):c.74+1276T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 167,334 control chromosomes in the GnomAD database, including 1,529 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1366 hom., cov: 32)

Exomes 𝑓: 0.12 ( 163 hom. )

Consequence

CASP2
NM_032982.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.121

Publications

8 publications found

Variant links:

Genes affected

CASP2 (HGNC:1503): (caspase 2) This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Caspases mediate cellular apoptosis through the proteolytic cleavage of specific protein substrates. The encoded protein may function in stress-induced cell death pathways, cell cycle maintenance, and the suppression of tumorigenesis. Increased expression of this gene may play a role in neurodegenerative disorders including Alzheimer's disease, Huntington's disease and temporal lobe epilepsy. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jan 2011]

CASP2 Gene-Disease associations (from GenCC):

intellectual developmental disorder, autosomal recessive 80, with variant lissencephaly
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

CASP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CASP2	NM_032982.4 link	c.74+1276T>G	intron_variant	Intron 1 of 10	ENST00000310447.10	NP_116764.2	P42575-1A0A0S2Z3H1
CASP2	NM_001224.5 link	c.-20+149T>G	intron_variant	Intron 1 of 11		NP_001215.1	P42575D3DXD9
CASP2	NM_032983.4 link	c.74+1276T>G	intron_variant	Intron 1 of 9		NP_116765.2	P42575A0A087WYM1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP2	ENST00000310447.10 link	c.74+1276T>G		intron_variant	Intron 1 of 10	1	NM_032982.4	ENSP00000312664.5		P42575-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17529

AN:

152104

Hom.:

1368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0316

Gnomad AMI

AF:

0.174

Gnomad AMR

AF:

0.0831

Gnomad ASJ

AF:

0.118

Gnomad EAS

AF:

0.0110

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.167

Gnomad OTH

AF:

0.0989

GnomAD4 exome

AF:

0.120

AC:

1815

AN:

15112

Hom.:

163

AF XY:

0.121

AC XY:

890

AN XY:

7370

show subpopulations

African (AFR)

AF:

0.0246

AC:

AN:

284

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.0588

AC:

AN:

102

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.123

AC:

AN:

300

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.0938

AC:

AN:

European-Non Finnish (NFE)

AF:

0.124

AC:

1710

AN:

13806

Other (OTH)

AF:

0.102

AC:

AN:

510

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

155

232

310

387

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

176

264

352

440

<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:

0.115

AC:

17526

AN:

152222

Hom.:

1366

Cov.:

AF XY:

0.116

AC XY:

8667

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.0314

AC:

1307

AN:

41562

American (AMR)

AF:

0.0829

AC:

1267

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.118

AC:

411

AN:

3472

East Asian (EAS)

AF:

0.0110

AC:

AN:

5180

South Asian (SAS)

AF:

0.150

AC:

724

AN:

4824

European-Finnish (FIN)

AF:

0.189

AC:

1995

AN:

10566

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.167

AC:

11382

AN:

68010

Other (OTH)

AF:

0.0978

AC:

207

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

783

1565

2348

3130

3913

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

202

404

606

808

1010

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

3106

Bravo

AF:

0.101

Asia WGS

AF:

0.0880

AC:

305

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

4.0

(source)

DANN

Benign

0.59

PhyloP100

0.12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over