rs3900115

Positions:

chr2-201185954-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_032977.4(CASP10):c.177A>G(p.Ser59=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,613,588 control chromosomes in the GnomAD database, including 203,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.48 ( 18041 hom., cov: 31)

Exomes 𝑓: 0.50 ( 185337 hom. )

Consequence

CASP10
NM_032977.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9O:1

Conservation

PhyloP100: -0.715

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 2-201185954-A-G is Benign according to our data. Variant chr2-201185954-A-G is described in ClinVar as [Benign]. Clinvar id is 333418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-201185954-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.715 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP10	NM_032977.4 linkuse as main transcript	c.177A>G	p.Ser59=	synonymous_variant	2/10	ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11 linkuse as main transcript	c.177A>G	p.Ser59=	synonymous_variant	2/10	1	NM_032977.4	ENSP00000286186	P2	Q92851-4

Frequencies

GnomAD3 genomes

AF:

0.483

AC:

73309

AN:

151912

Hom.:

18023

Cov.:

show subpopulations

Gnomad AFR

AF:

0.484

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.418

Gnomad ASJ

AF:

0.526

Gnomad EAS

AF:

0.222

Gnomad SAS

AF:

0.333

Gnomad FIN

AF:

0.511

Gnomad MID

AF:

0.383

Gnomad NFE

AF:

0.522

Gnomad OTH

AF:

0.465

GnomAD3 exomes

AF:

0.448

AC:

112498

AN:

250972

Hom.:

26409

AF XY:

0.448

AC XY:

60819

AN XY:

135654

show subpopulations

Gnomad AFR exome

AF:

0.483

Gnomad AMR exome

AF:

0.349

Gnomad ASJ exome

AF:

0.515

Gnomad EAS exome

AF:

0.226

Gnomad SAS exome

AF:

0.352

Gnomad FIN exome

AF:

0.500

Gnomad NFE exome

AF:

0.519

Gnomad OTH exome

AF:

0.466

GnomAD4 exome

AF:

0.498

AC:

727762

AN:

1461558

Hom.:

185337

Cov.:

AF XY:

0.494

AC XY:

359307

AN XY:

727076

show subpopulations

Gnomad4 AFR exome

AF:

0.486

Gnomad4 AMR exome

AF:

0.360

Gnomad4 ASJ exome

AF:

0.522

Gnomad4 EAS exome

AF:

0.197

Gnomad4 SAS exome

AF:

0.355

Gnomad4 FIN exome

AF:

0.499

Gnomad4 NFE exome

AF:

0.526

Gnomad4 OTH exome

AF:

0.483

GnomAD4 genome

AF:

0.483

AC:

73370

AN:

152030

Hom.:

18041

Cov.:

AF XY:

0.476

AC XY:

35338

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.484

Gnomad4 AMR

AF:

0.417

Gnomad4 ASJ

AF:

0.526

Gnomad4 EAS

AF:

0.222

Gnomad4 SAS

AF:

0.334

Gnomad4 FIN

AF:

0.511

Gnomad4 NFE

AF:

0.522

Gnomad4 OTH

AF:

0.472

Alfa

AF:

0.508

Hom.:

39509

Bravo

AF:

0.474

Asia WGS

AF:

0.301

AC:

1048

AN:

3478

EpiCase

AF:

0.506

EpiControl

AF:

0.516

ClinVar

Significance: Benign

Submissions summary: Benign:9Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Mar 29, 2016	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Nov 12, 2023	This variant is classified as Benign based on local population frequency. This variant was detected in 68% of patients studied by a panel of primary immunodeficiencies. Number of patients: 65. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

Autoimmune lymphoproliferative syndrome type 2A

Benign:3

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 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. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:2Other:1

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
not provided, no classification provided	phenotyping only	GenomeConnect, ClinGen	-	Variant interpreted as Benign and reported on 04-27-2020 by Lab or GTR ID 500031. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. This variant was reported in an individual referred for clinical diagnostic genetic testing. -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.78

DANN

Benign

0.50

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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