7-143288526-G-C

Variant names:

• chr7-143288526-G-C
• rs368981317
• NM_032982.4:c.71G>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032982.4(CASP2):​c.71G>C​(p.Arg24Pro) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP2 NM_032982.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.26

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36768478).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP2	NM_032982.4	c.71G>C	p.Arg24Pro	missense_variant	Exon 1 of 11	ENST00000310447.10	NP_116764.2
CASP2	NM_032983.4	c.71G>C	p.Arg24Pro	missense_variant	Exon 1 of 10		NP_116765.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP2	ENST00000310447.10	c.71G>C	p.Arg24Pro	missense_variant	Exon 1 of 11	1	NM_032982.4	ENSP00000312664.5
CASP2	ENST00000619992.4	c.71G>C	p.Arg24Pro	missense_variant	Exon 1 of 10	1		ENSP00000481929.1
CASP2	ENST00000350623.7	n.71G>C		non_coding_transcript_exon_variant	Exon 1 of 10	1		ENSP00000340030.3
CASP2	ENST00000392925.6	c.71G>C	p.Arg24Pro	missense_variant	Exon 1 of 5	3		ENSP00000376656.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.035	T
BayesDel_noAF	Benign	-0.29
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.013	T;T;T
Eigen	Benign	0.0050
Eigen_PC	Benign	0.055
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.37	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.97	.;L;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	0.12	.;N;N
REVEL	Benign	0.15
Sift	Benign	0.067	.;T;D
Sift4G	Uncertain	0.043	D;D;D
Polyphen		0.61	.;P;.
Vest4		0.41
MutPred		0.57		Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);Loss of MoRF binding (P = 0.007);
MVP		0.83
MPC		0.86
ClinPred		0.94	D
GERP RS		4.3
Varity_R		0.29
gMVP		0.43

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

LitVar

Other links and lift over

dbSNP: rs368981317; hg19: chr7-142985619;