2-201209805-A-G

Variant names:

• chr2-201209805-A-G
• rs7576306
• NM_032977.4:c.1415+243A>G

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.1415+243A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 151,798 control chromosomes in the GnomAD database, including 11,909 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.37 (11909 hom., cov: 30)
• Consequence: CASP10 NM_032977.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.61
• Publications: 9 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=-0.86).
• BP6: Variant 2-201209805-A-G is Benign according to our data. Variant chr2-201209805-A-G is described in ClinVar as [Benign]. Clinvar id is 1274829.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASP10	NM_032977.4	c.1415+243A>G		intron_variant	Intron 9 of 9	ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11	c.1415+243A>G		intron_variant	Intron 9 of 9	1	NM_032977.4	ENSP00000286186.6

Frequencies

GnomAD3 genomes AF: 0.372 AC: 56437 AN: 151680 Hom.: 11910 Cov.: 30

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.211

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.483

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.372 AC: 56441 AN: 151798 Hom.: 11909 Cov.: 30 AF XY: 0.366 AC XY: 27166 AN XY: 74146

African (AFR) AF: 0.185 AC: 7661 AN: 41408

American (AMR) AF: 0.368 AC: 5609 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1510 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1081 AN: 5140

South Asian (SAS) AF: 0.270 AC: 1293 AN: 4790

European-Finnish (FIN) AF: 0.483 AC: 5082 AN: 10520

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.485 AC: 32916 AN: 67926

Other (OTH) AF: 0.392 AC: 824 AN: 2104

Alfa AF: 0.448 Hom.: 18522

Bravo AF: 0.358

Asia WGS AF: 0.222 AC: 773 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 25, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.5
DANN	Benign	0.73
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7576306; hg19: chr2-202074528;