2-201185430-G-A

Variant names:

• chr2-201185430-G-A
• rs41351447
• NM_032977.4:c.-7-341G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032977.4(CASP10):​c.-7-341G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.044 in 152,148 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.044 (188 hom., cov: 32)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.694
• Publications: 2 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), ClinGen, G2P
• autoimmune lymphoproliferative syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 2-201185430-G-A is Benign according to our data. Variant chr2-201185430-G-A is described in ClinVar as Benign. ClinVar VariationId is 1296629.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0593 is higher than 0.05.

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.-7-341G>A		intron	N/A	NP_116759.2
	CASP10	NM_032974.5		c.-7-341G>A		intron	N/A	NP_116756.2
	CASP10	NM_001230.5		c.-7-341G>A		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.-7-341G>A		intron	N/A	ENSP00000286186.6	Q92851-4
	CASP10	ENST00000448480.1	TSL:1	c.-7-341G>A		intron	N/A	ENSP00000396835.1	Q92851-5
	CASP10	ENST00000313728.12	TSL:1	c.-7-341G>A		intron	N/A	ENSP00000314599.7	Q92851-6

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 6655 AN: 152030 Hom.: 179 Cov.: 32

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.00771

Gnomad AMR AF: 0.0255

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.00308

Gnomad SAS AF: 0.0609

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0392

Gnomad OTH AF: 0.0339

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

GnomAD4 genome AF: 0.0440 AC: 6692 AN: 152148 Hom.: 188 Cov.: 32 AF XY: 0.0436 AC XY: 3245 AN XY: 74386

African (AFR) AF: 0.0613 AC: 2545 AN: 41496

American (AMR) AF: 0.0255 AC: 389 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 317 AN: 3468

East Asian (EAS) AF: 0.00309 AC: 16 AN: 5184

South Asian (SAS) AF: 0.0603 AC: 291 AN: 4826

European-Finnish (FIN) AF: 0.0328 AC: 347 AN: 10578

Middle Eastern (MID) AF: 0.0952 AC: 28 AN: 294

European-Non Finnish (NFE) AF: 0.0392 AC: 2663 AN: 68010

Other (OTH) AF: 0.0421 AC: 89 AN: 2116

Alfa AF: 0.0452 Hom.: 15

Bravo AF: 0.0408

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.56
PhyloP100		0.69
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: rs41351447; hg19: chr2-202050153;