chr2-201211725-T-C

Variant names:

• chr2-201211725-T-C
• rs6435068
• NM_032977.4:c.1415+2163T>C

Variant summary

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

The NM_032977.4(CASP10):​c.1415+2163T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,188 control chromosomes in the GnomAD database, including 2,519 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 (2519 hom., cov: 32)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.95
• Publications: 4 publications found

Genes affected

CASP10 (HGNC:1500): (caspase 10) This gene encodes a protein which is a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This protein cleaves and activates caspases 3 and 7, and the protein itself is processed by caspase 8. Mutations in this gene are associated with type IIA autoimmune lymphoproliferative syndrome, non-Hodgkin lymphoma and gastric cancer. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Apr 2011]

CASP10 Gene-Disease associations (from GenCC):

• autoimmune lymphoproliferative syndrome type 2A

  Inheritance: Unknown, AD Classification: STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.336 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP10	NM_032977.4	c.1415+2163T>C		intron_variant	Intron 9 of 9	ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11	c.1415+2163T>C		intron_variant	Intron 9 of 9	1	NM_032977.4	ENSP00000286186.6

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18813 AN: 152070 Hom.: 2498 Cov.: 32

Gnomad AFR AF: 0.340

Gnomad AMI AF: 0.00769

Gnomad AMR AF: 0.0571

Gnomad ASJ AF: 0.0913

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0615

Gnomad FIN AF: 0.0327

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.0397

Gnomad OTH AF: 0.0886

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.124 AC: 18889 AN: 152188 Hom.: 2519 Cov.: 32 AF XY: 0.121 AC XY: 8994 AN XY: 74424

African (AFR) AF: 0.340 AC: 14099 AN: 41442

American (AMR) AF: 0.0570 AC: 872 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0913 AC: 317 AN: 3472

East Asian (EAS) AF: 0.00366 AC: 19 AN: 5186

South Asian (SAS) AF: 0.0609 AC: 294 AN: 4826

European-Finnish (FIN) AF: 0.0327 AC: 347 AN: 10620

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0397 AC: 2700 AN: 68026

Other (OTH) AF: 0.0962 AC: 203 AN: 2110

Alfa AF: 0.0930 Hom.: 187

Bravo AF: 0.131

Asia WGS AF: 0.0740 AC: 256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.53
DANN	Benign	0.46
PhyloP100		-2.0
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

Other links and lift over

dbSNP: rs6435068; hg19: chr2-202076448;