12-9688007-C-T

Variant names:

• chr12-9688007-C-T
• rs757072519
• NM_013269.6:c.278C>T

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.278C>T​(p.Thr93Ile) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T93N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: CLEC2D NM_013269.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 0 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=0.09476641).

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.278C>T	p.Thr93Ile	missense	Exon 3 of 5	NP_037401.1	Q9UHP7-1
	CLEC2D	NM_001004419.5		c.278C>T	p.Thr93Ile	missense	Exon 3 of 6	NP_001004419.1	Q9UHP7-3
	CLEC2D	NM_001197317.3		c.167C>T	p.Thr56Ile	missense	Exon 2 of 4	NP_001184246.1	W8JXM2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CLEC2D	ENST00000290855.11	TSL:1 MANE Select	c.278C>T	p.Thr93Ile	missense	Exon 3 of 5	ENSP00000290855.6	Q9UHP7-1
	CLEC2D	ENST00000261340.11	TSL:1	c.278C>T	p.Thr93Ile	missense	Exon 3 of 6	ENSP00000261340.7	Q9UHP7-3
	CLEC2D	ENST00000430909.5	TSL:1	c.215C>T	p.Thr72Ile	missense	Exon 2 of 5	ENSP00000413045.1	A0A0C4DG81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	1.8
DANN	Benign	0.97
DEOGEN2	Benign	0.043	T
Eigen	Benign	-0.85
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.0045	N
LIST_S2	Benign	0.63	T
M_CAP	Benign	0.0034	T
MetaRNN	Benign	0.095	T
MetaSVM	Benign	-0.85	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		-0.29
PrimateAI	Benign	0.31	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.11
Sift	Benign	0.25	T
Sift4G	Benign	0.32	T
Polyphen		0.48	P
Vest4		0.10
MutPred		0.44		Gain of catalytic residue at S90 (P = 0.0073)
MVP		0.068
MPC		0.12
ClinPred		0.99	D
GERP RS		-3.4
PromoterAI		0.15	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.21
gMVP		0.19
Mutation Taster		=89/11	polymorphism

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

Other links and lift over

dbSNP: rs757072519; hg19: chr12-9840603;