Genetic Variant NM_032982.4: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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