rs373703940

Variant names:

• chr12-9857553-T-A
• rs373703940
• NM_005127.3:c.158A>T

Your query was ambiguous. Multiple possible variants found:

• chr12-9857553-T-A
• chr12-9857553-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_005127.3(CLEC2B):​c.158A>T​(p.Glu53Val) 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. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E53G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC2B NM_005127.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.135
• Publications: 0 publications found

Genes affected

CLEC2B (HGNC:2053): (C-type lectin domain family 2 member B) This gene encodes a member of the C-type lectin/C-type lectin-like domain (CTL/CTLD) superfamily. Members of this family share a common protein fold and have diverse functions, such as cell adhesion, cell-cell signalling, glycoprotein turnover, and roles in inflammation and immune response. The encoded type 2 transmembrane protein may function as a cell activation antigen. An alternative splice variant has been described but its full-length sequence has not been determined. This gene is closely linked to other CTL/CTLD superfamily members on chromosome 12p13 in the natural killer gene complex region. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13386583).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005127.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2B	NM_005127.3	MANE Select	c.158A>T	p.Glu53Val	missense	Exon 3 of 5	NP_005118.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2B	ENST00000228438.3	TSL:1 MANE Select	c.158A>T	p.Glu53Val	missense	Exon 3 of 5	ENSP00000228438.2	Q92478
	CLEC2B	ENST00000539028.1	TSL:1	n.235A>T		non_coding_transcript_exon	Exon 2 of 2
	CLEC2B	ENST00000540743.1	TSL:1	n.342A>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.37
BayesDel_addAF	Benign	-0.031	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.094
DEOGEN2	Benign	0.19	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-0.96
FATHMM_MKL	Benign	0.014	N
LIST_S2	Benign	0.28	T
M_CAP	Benign	0.0077	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.14
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.5	N
REVEL	Benign	0.094
Sift	Uncertain	0.019	D
Sift4G	Benign	1.0	T
Polyphen		0.14	B
Vest4		0.34
MutPred		0.45		Gain of catalytic residue at E53 (P = 2e-04)
MVP		0.56
MPC		0.18
ClinPred		0.14	T
GERP RS		1.6
Varity_R		0.14
gMVP		0.61
Mutation Taster		=92/8	polymorphism

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: rs373703940; hg19: chr12-10010152;