chr2-201183496-C-T

Position:

• chr2-201183496-C-T

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.-8+188C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.039 in 152,126 control chromosomes in the GnomAD database, including 147 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: 𝑓 0.039 (147 hom., cov: 32)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.82

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=-0.82).
• BP6: Variant 2-201183496-C-T is Benign according to our data. Variant chr2-201183496-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1706792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0533 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP10	NM_032977.4	c.-8+188C>T		intron_variant		ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11	c.-8+188C>T		intron_variant		1	NM_032977.4	ENSP00000286186	P2

Frequencies

GnomAD3 genomes AF: 0.0388 AC: 5903 AN: 152008 Hom.: 139 Cov.: 32

Gnomad AFR AF: 0.0454

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0226

Gnomad ASJ AF: 0.0888

Gnomad EAS AF: 0.00366

Gnomad SAS AF: 0.0595

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0387

Gnomad OTH AF: 0.0273

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

GnomAD4 genome AF: 0.0390 AC: 5929 AN: 152126 Hom.: 147 Cov.: 32 AF XY: 0.0390 AC XY: 2899 AN XY: 74368

Gnomad4 AFR AF: 0.0456

Gnomad4 AMR AF: 0.0226

Gnomad4 ASJ AF: 0.0888

Gnomad4 EAS AF: 0.00367

Gnomad4 SAS AF: 0.0589

Gnomad4 FIN AF: 0.0328

Gnomad4 NFE AF: 0.0387

Gnomad4 OTH AF: 0.0355

Alfa AF: 0.0407 Hom.: 25

Bravo AF: 0.0353

Asia WGS AF: 0.0480 AC: 169 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 10, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.30
DANN	Benign	0.80

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: rs17860398; hg19: chr2-202048219;