rs13010627

Positions:

chr2-201209375-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032977.4(CASP10):c.1228G>A(p.Val410Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0567 in 1,614,048 control chromosomes in the GnomAD database, including 3,002 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.042 ( 175 hom., cov: 31)

Exomes 𝑓: 0.058 ( 2827 hom. )

Consequence

CASP10
NM_032977.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6O:1

Conservation

PhyloP100: 0.528

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017305046).

BP6

Variant 2-201209375-G-A is Benign according to our data. Variant chr2-201209375-G-A is described in ClinVar as [Benign]. Clinvar id is 21727.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-201209375-G-A is described in Lovd as [Benign]. Variant chr2-201209375-G-A is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0632 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP10	NM_032977.4 link	c.1228G>A	p.Val410Ile	missense_variant	9/10	ENST00000286186.11	NP_116759.2	Q92851-4A0A0S2Z3Z5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11 link	c.1228G>A	p.Val410Ile	missense_variant	9/10	1	NM_032977.4	ENSP00000286186.6		Q92851-4

Frequencies

GnomAD3 genomes

AF:

0.0420

AC:

6382

AN:

152054

Hom.:

175

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0123

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.0361

Gnomad ASJ

AF:

0.0392

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00601

Gnomad FIN

AF:

0.0573

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0649

Gnomad OTH

AF:

0.0464

GnomAD3 exomes

AF:

0.0419

AC:

10531

AN:

251078

Hom.:

322

AF XY:

0.0425

AC XY:

5767

AN XY:

135702

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.0274

Gnomad ASJ exome

AF:

0.0413

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0106

Gnomad FIN exome

AF:

0.0509

Gnomad NFE exome

AF:

0.0642

Gnomad OTH exome

AF:

0.0470

GnomAD4 exome

AF:

0.0583

AC:

85185

AN:

1461876

Hom.:

2827

Cov.:

AF XY:

0.0569

AC XY:

41407

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.00917

Gnomad4 AMR exome

AF:

0.0286

Gnomad4 ASJ exome

AF:

0.0420

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.0102

Gnomad4 FIN exome

AF:

0.0565

Gnomad4 NFE exome

AF:

0.0678

Gnomad4 OTH exome

AF:

0.0513

GnomAD4 genome

AF:

0.0419

AC:

6381

AN:

152172

Hom.:

175

Cov.:

AF XY:

0.0389

AC XY:

2897

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.0122

Gnomad4 AMR

AF:

0.0360

Gnomad4 ASJ

AF:

0.0392

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00622

Gnomad4 FIN

AF:

0.0573

Gnomad4 NFE

AF:

0.0648

Gnomad4 OTH

AF:

0.0459

Alfa

AF:

0.0580

Hom.:

526

Bravo

AF:

0.0400

TwinsUK

AF:

0.0690

AC:

256

ALSPAC

AF:

0.0729

AC:

281

ESP6500AA

AF:

0.0159

AC:

ESP6500EA

AF:

0.0659

AC:

567

ExAC

AF:

0.0425

AC:

5165

Asia WGS

AF:

0.00577

AC:

AN:

3478

EpiCase

AF:

0.0623

EpiControl

AF:

0.0640

ClinVar

Significance: Benign

Submissions summary: Benign:6Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 15, 2019	This variant is associated with the following publications: (PMID: 16251207, 10755819, 10412980, 19423537, 20978178, 20981092, 16446975, 31309545, 11973654) -

Autoimmune lymphoproliferative syndrome type 2A

Benign:2Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Mar 06, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not specified

Benign:1

Benign, no assertion criteria provided

clinical testing

Genome Diagnostics Laboratory, University Medical Center Utrecht

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.70

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.041

.;T;.;.;.

Eigen

Benign

-0.64

Eigen_PC

Benign

-0.78

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.68

T;T;T;T;D

MetaRNN

Benign

0.017

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

L;L;.;.;.

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.71

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.11

T;T;T;T;T

Sift4G

Benign

0.19

T;T;T;T;T

Polyphen

0.99

D;D;D;P;D

Vest4

0.026

MPC

0.15

ClinPred

0.0077

GERP RS

2.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.080

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over