2-201221942-G-A

Position:

• chr2-201221942-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_032974.5(CASP10):​c.1416-6991G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0447 in 152,250 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.045 (213 hom., cov: 32)
• Consequence: CASP10 NM_032974.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0666 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP10	NM_032974.5	c.1416-6991G>A		intron_variant			NP_116756.2
CASP10	NM_001206542.2	c.1287-6991G>A		intron_variant			NP_001193471.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000448480.1	c.1287-6991G>A		intron_variant		1		ENSP00000396835.1
CASP10	ENST00000272879.9	c.1416-6991G>A		intron_variant		2		ENSP00000272879.5
CASP10	ENST00000696199.1	c.722-6988G>A		intron_variant				ENSP00000512481.1

Frequencies

GnomAD3 genomes AF: 0.0447 AC: 6798 AN: 152132 Hom.: 213 Cov.: 32

Gnomad AFR AF: 0.0118

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.0563

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.000385

Gnomad SAS AF: 0.00912

Gnomad FIN AF: 0.0393

Gnomad MID AF: 0.0613

Gnomad NFE AF: 0.0682

Gnomad OTH AF: 0.0522

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

GnomAD4 genome AF: 0.0447 AC: 6799 AN: 152250 Hom.: 213 Cov.: 32 AF XY: 0.0431 AC XY: 3205 AN XY: 74446

Gnomad4 AFR AF: 0.0118

Gnomad4 AMR AF: 0.0563

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.00892

Gnomad4 FIN AF: 0.0393

Gnomad4 NFE AF: 0.0683

Gnomad4 OTH AF: 0.0511

Alfa AF: 0.0590 Hom.: 65

Bravo AF: 0.0457

Asia WGS AF: 0.00779 AC: 28 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.58
DANN	Benign	0.41

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs41373151; hg19: chr2-202086665;