chr2-201208426-C-T

Variant names:

• chr2-201208426-C-T
• rs6750157
• NM_032977.4:c.922+243C>T

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.922+243C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 963,430 control chromosomes in the GnomAD database, including 1,337 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.062 (946 hom., cov: 31)
  • Exomes 𝑓: 0.0048 (391 hom.)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.79
• Publications: 1 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), 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=-0.99).
• BP6: Variant 2-201208426-C-T is Benign according to our data. Variant chr2-201208426-C-T is described in ClinVar as Benign. ClinVar VariationId is 1243974.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP10	NM_032977.4	MANE Select	c.922+243C>T		intron	N/A	NP_116759.2
	CASP10	NM_032974.5		c.922+243C>T		intron	N/A	NP_116756.2
	CASP10	NM_001230.5		c.793+243C>T		intron	N/A	NP_001221.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CASP10	ENST00000286186.11	TSL:1 MANE Select	c.922+243C>T		intron	N/A	ENSP00000286186.6
	CASP10	ENST00000448480.1	TSL:1	c.793+243C>T		intron	N/A	ENSP00000396835.1
	CASP10	ENST00000313728.12	TSL:1	c.722-644C>T		intron	N/A	ENSP00000314599.7

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9344 AN: 151946 Hom.: 944 Cov.: 31

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000794

Gnomad OTH AF: 0.0463

GnomAD4 exome AF: 0.00480 AC: 3891 AN: 811366 Hom.: 391 Cov.: 14 AF XY: 0.00442 AC XY: 1658 AN XY: 375420

African (AFR) AF: 0.219 AC: 3378 AN: 15410

American (AMR) AF: 0.0209 AC: 20 AN: 956

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5014

East Asian (EAS) AF: 0.000286 AC: 1 AN: 3498

South Asian (SAS) AF: 0.000375 AC: 6 AN: 15994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 270

Middle Eastern (MID) AF: 0.00769 AC: 12 AN: 1560

European-Non Finnish (NFE) AF: 0.000245 AC: 182 AN: 742018

Other (OTH) AF: 0.0110 AC: 292 AN: 26646

GnomAD4 genome AF: 0.0616 AC: 9368 AN: 152064 Hom.: 946 Cov.: 31 AF XY: 0.0596 AC XY: 4429 AN XY: 74358

African (AFR) AF: 0.214 AC: 8850 AN: 41428

American (AMR) AF: 0.0234 AC: 358 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10578

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 67996

Other (OTH) AF: 0.0458 AC: 97 AN: 2116

Alfa AF: 0.0495 Hom.: 74

Bravo AF: 0.0697

Asia WGS AF: 0.0110 AC: 39 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Feb 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.024
DANN	Benign	0.46
PhyloP100		-3.8
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: rs6750157; hg19: chr2-202073149;