2-201185859-G-C

Position:

• chr2-201185859-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_032977.4(CASP10):​c.82G>C​(p.Asp28His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CASP10 NM_032977.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0730

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 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3827675).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CASP10	NM_032977.4	c.82G>C	p.Asp28His	missense_variant	2/10	ENST00000286186.11	NP_116759.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CASP10	ENST00000286186.11	c.82G>C	p.Asp28His	missense_variant	2/10	1	NM_032977.4	ENSP00000286186.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Autoimmune lymphoproliferative syndrome type 2A Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 27, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.0084	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.54	.;.;D;.;.;.;.
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.41
FATHMM_MKL	Benign	0.064	N
LIST_S2	Uncertain	0.91	D;D;D;D;D;D;D
M_CAP	Benign	0.051	D
MetaRNN	Benign	0.38	T;T;T;T;T;T;T
MetaSVM	Benign	-0.30	T
MutationAssessor	Uncertain	2.1	M;M;M;M;M;M;M
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-3.6	D;D;D;D;D;D;D
REVEL	Benign	0.28
Sift	Uncertain	0.0090	D;D;D;D;T;D;D
Sift4G	Benign	0.091	T;D;T;D;T;T;T
Polyphen		0.99	D;.;D;.;D;D;D
Vest4		0.14
MutPred		0.68		Loss of ubiquitination at K23 (P = 0.0505);Loss of ubiquitination at K23 (P = 0.0505);Loss of ubiquitination at K23 (P = 0.0505);Loss of ubiquitination at K23 (P = 0.0505);Loss of ubiquitination at K23 (P = 0.0505);Loss of ubiquitination at K23 (P = 0.0505);Loss of ubiquitination at K23 (P = 0.0505);
MVP		0.96
MPC		0.43
ClinPred		0.84	D
GERP RS		2.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.27
gMVP		0.41

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-202050582;