12-9681032-C-G

Variant names:

• chr12-9681032-C-G
• rs3764021
• NM_013269.6:c.171C>G

Variant summary

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

The NM_013269.6(CLEC2D):​c.171C>G​(p.Ser57Arg) variant causes a missense, splice region 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. 16/24 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC2D NM_013269.6 missense, splice_region
• Scores: Splicing: ADA: 0.0002127
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.588
• Publications: 85 publications found

Genes affected

CLEC2D (HGNC:14351): (C-type lectin domain family 2 member D) This gene encodes a member of the natural killer cell receptor C-type lectin family. The encoded protein inhibits osteoclast formation and contains a transmembrane domain near the N-terminus as well as the C-type lectin-like extracellular domain. Several alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Oct 2010]

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=0.1113247).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013269.6. 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
	CLEC2D	NM_013269.6	MANE Select	c.171C>G	p.Ser57Arg	missense splice_region	Exon 2 of 5	NP_037401.1	Q9UHP7-1
	CLEC2D	NM_001004419.5		c.171C>G	p.Ser57Arg	missense splice_region	Exon 2 of 6	NP_001004419.1	Q9UHP7-3
	CLEC2D	NM_001197318.3		c.171C>G	p.Ser57Arg	missense splice_region	Exon 2 of 4	NP_001184247.1	Q9UHP7-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2D	ENST00000290855.11	TSL:1 MANE Select	c.171C>G	p.Ser57Arg	missense splice_region	Exon 2 of 5	ENSP00000290855.6	Q9UHP7-1
	CLEC2D	ENST00000261340.11	TSL:1	c.171C>G	p.Ser57Arg	missense splice_region	Exon 2 of 6	ENSP00000261340.7	Q9UHP7-3
	CLEC2D	ENST00000430909.5	TSL:1	c.108C>G	p.Ser36Arg	missense splice_region	Exon 1 of 5	ENSP00000413045.1	A0A0C4DG81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 82256

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	0.073
DANN	Uncertain	0.98
DEOGEN2	Benign	0.0097	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0052	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0017	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.7	L
PhyloP100		-0.59
PrimateAI	Benign	0.37	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.12
Sift	Benign	0.34	T
Sift4G	Benign	0.43	T
Polyphen		1.0	D
Vest4		0.19
MutPred		0.59		Gain of catalytic residue at M52 (P = 0)
MVP		0.068
MPC		0.11
ClinPred		0.50	T
GERP RS		-2.4
PromoterAI		-0.032	Neutral
Varity_R		0.044
gMVP		0.29
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00021
dbscSNV1_RF	Benign	0.11
SpliceAI score (max)		0.040		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: rs3764021; hg19: chr12-9833628;