12-9853391-C-T

Variant names:

• chr12-9853391-C-T
• NM_005127.3:c.359G>A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_005127.3(CLEC2B):​c.359G>A​(p.Ser120Asn) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC2B NM_005127.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.48

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

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03225988).
• BP6: Variant 12-9853391-C-T is Benign according to our data. Variant chr12-9853391-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2485001.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC2B	NM_005127.3	c.359G>A	p.Ser120Asn	missense_variant	Exon 5 of 5	ENST00000228438.3	NP_005118.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC2B	ENST00000228438.3	c.359G>A	p.Ser120Asn	missense_variant	Exon 5 of 5	1	NM_005127.3	ENSP00000228438.2
CLEC2B	ENST00000538152.1	c.152G>A	p.Ser51Asn	missense_variant	Exon 2 of 2	2		ENSP00000437946.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Feb 15, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.015
DANN	Benign	0.47
DEOGEN2	Benign	0.026	T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00094	N
LIST_S2	Benign	0.22	T;T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.032	T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Benign	-0.83	N;.
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-0.010	N;N
REVEL	Benign	0.0050
Sift	Benign	0.98	T;T
Sift4G	Benign	0.94	T;T
Polyphen		0.0040	B;.
Vest4		0.042
MutPred		0.35		Gain of catalytic residue at F115 (P = 6e-04);.;
MVP		0.085
MPC		0.14
ClinPred		0.024	T
GERP RS		-3.5
Varity_R		0.017
gMVP		0.39

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: chr12-10005990;