12-9926268-A-G

Position:

• chr12-9926268-A-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001130711.2(CLEC2A):​c.131T>C​(p.Ile44Thr) 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. 15/20 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: CLEC2A NM_001130711.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.379

Genes affected

CLEC2A (HGNC:24191): (C-type lectin domain family 2 member A) Enables protein homodimerization activity. Predicted to be involved in natural killer cell mediated cytotoxicity. Predicted to act upstream of or within several processes, including T cell receptor signaling pathway; regulation of actin filament polymerization; and regulation of interleukin-2 production. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06286201).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLEC2A	NM_001130711.2	c.131T>C	p.Ile44Thr	missense_variant	2/5	ENST00000455827.2	NP_001124183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLEC2A	ENST00000455827.2	c.131T>C	p.Ile44Thr	missense_variant	2/5	1	NM_001130711.2	ENSP00000396163	P1
CLEC2A	ENST00000339766.8	c.131T>C	p.Ile44Thr	missense_variant	2/5	1		ENSP00000339732

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.131T>C (p.I44T) alteration is located in exon 2 (coding exon 2) of the CLEC2A gene. This alteration results from a T to C substitution at nucleotide position 131, causing the isoleucine (I) at amino acid position 44 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.74
DANN	Benign	0.63
DEOGEN2	Benign	0.0058	.;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.013	N
LIST_S2	Benign	0.33	T;T
M_CAP	Benign	0.00074	T
MetaRNN	Benign	0.063	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	0.81	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.040	N;N
REVEL	Benign	0.016
Sift	Benign	0.14	T;T
Sift4G	Uncertain	0.019	D;D
Polyphen		0.028	B;B
Vest4		0.058
MutPred		0.52		Gain of catalytic residue at V41 (P = 0);Gain of catalytic residue at V41 (P = 0);
MVP		0.076
ClinPred		0.068	T
GERP RS		-3.3
Varity_R		0.038
gMVP		0.063

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: chr12-10078867;