rs41343445

Variant names:

• chr2-201202990-A-G
• rs41343445
• NM_032977.4:c.685-740A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_032977.4(CASP10):​c.685-740A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 152,290 control chromosomes in the GnomAD database, including 3 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 0.0048 (3 hom., cov: 32)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 1 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: AD, Unknown Classification: STRONG, LIMITED Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BS2: High AC in GnomAd4 at 730 AD,Unknown gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032977.4. 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
	CASP10	NM_032977.4	MANE Select	c.685-740A>G		intron	N/A	NP_116759.2
	CASP10	NM_032974.5		c.685-740A>G		intron	N/A	NP_116756.2
	CASP10	NM_001230.5		c.685-5085A>G		intron	N/A	NP_001221.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP10	ENST00000286186.11	TSL:1 MANE Select	c.685-740A>G		intron	N/A	ENSP00000286186.6	Q92851-4
	CASP10	ENST00000448480.1	TSL:1	c.685-5085A>G		intron	N/A	ENSP00000396835.1	Q92851-5
	CASP10	ENST00000313728.12	TSL:1	c.685-740A>G		intron	N/A	ENSP00000314599.7	Q92851-6

Frequencies

GnomAD3 genomes AF: 0.00480 AC: 730 AN: 152172 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00138

Gnomad AMI AF: 0.00548

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00547

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00565

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00757

Gnomad OTH AF: 0.00478

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

GnomAD4 genome AF: 0.00479 AC: 730 AN: 152290 Hom.: 3 Cov.: 32 AF XY: 0.00431 AC XY: 321 AN XY: 74468

African (AFR) AF: 0.00137 AC: 57 AN: 41558

American (AMR) AF: 0.00418 AC: 64 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00547 AC: 19 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00565 AC: 60 AN: 10612

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00757 AC: 515 AN: 68016

Other (OTH) AF: 0.00473 AC: 10 AN: 2114

Alfa AF: 0.00572 Hom.: 0

Bravo AF: 0.00451

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.14
DANN	Benign	0.42
PhyloP100		-1.2
Mutation Taster		=100/0	polymorphism

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: rs41343445;

hg19: chr2-202067713;