rs3181166

Variant names:

• chr7-143289805-T-G
• rs3181166
• NM_032982.4:c.74+1276T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.121
• Publications: 8 publications found

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: Ambry Genetics, G2P

ACMG classification

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032982.4. 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
	CASP2	NM_032982.4	MANE Select	c.74+1276T>G		intron	N/A	NP_116764.2
	CASP2	NM_001224.5		c.-20+149T>G		intron	N/A	NP_001215.1
	CASP2	NM_032983.4		c.74+1276T>G		intron	N/A	NP_116765.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP2	ENST00000310447.10	TSL:1 MANE Select	c.74+1276T>G		intron	N/A	ENSP00000312664.5	P42575-1
	CASP2	ENST00000619992.4	TSL:1	c.74+1276T>G		intron	N/A	ENSP00000481929.1	A0A087WYM1
	CASP2	ENST00000350623.7	TSL:1	n.74+1276T>G		intron	N/A	ENSP00000340030.3	A0A087WYM1

Frequencies

GnomAD3 genomes AF: 0.115 AC: 17529 AN: 152104 Hom.: 1368 Cov.: 32

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

African (AFR) AF: 0.0246 AC: 7 AN: 284

American (AMR) AF: 0.00 AC: 0 AN: 10

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 6 AN: 102

East Asian (EAS) AF: 0.00 AC: 0 AN: 64

South Asian (SAS) AF: 0.123 AC: 37 AN: 300

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 4

Middle Eastern (MID) AF: 0.0938 AC: 3 AN: 32

European-Non Finnish (NFE) AF: 0.124 AC: 1710 AN: 13806

Other (OTH) AF: 0.102 AC: 52 AN: 510

GnomAD4 genome AF: 0.115 AC: 17526 AN: 152222 Hom.: 1366 Cov.: 32 AF XY: 0.116 AC XY: 8667 AN XY: 74430

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: 57 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: 18 AN: 294

European-Non Finnish (NFE) AF: 0.167 AC: 11382 AN: 68010

Other (OTH) AF: 0.0978 AC: 207 AN: 2116

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.0
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)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs3181166;

hg19: chr7-142986898;