2-201185430-G-A

Position:

• chr2-201185430-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CASP10	NM_032977.4	c.-7-341G>A		intron_variant		ENST00000286186.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CASP10	ENST00000286186.11	c.-7-341G>A		intron_variant		1	NM_032977.4	P2

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

Gnomad4 AFR AF: 0.0613

Gnomad4 AMR AF: 0.0255

Gnomad4 ASJ AF: 0.0914

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0603

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0392

Gnomad4 OTH AF: 0.0421

Alfa AF: 0.0452 Hom.: 15

Bravo AF: 0.0408

Asia WGS AF: 0.0560 AC: 196 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.6
DANN	Benign	0.56

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: rs41351447; hg19: chr2-202050153;