12-9688007-C-G

Variant names:

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

Variant summary

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

The NM_013269.6(CLEC2D):​c.278C>G​(p.Thr93Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000822 in 1,460,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/24 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)
  • Exomes 𝑓: 0.0000082 (0 hom.)
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>G	p.Thr93Ser	missense	Exon 3 of 5	NP_037401.1	Q9UHP7-1
	CLEC2D	NM_001004419.5		c.278C>G	p.Thr93Ser	missense	Exon 3 of 6	NP_001004419.1	Q9UHP7-3
	CLEC2D	NM_001197317.3		c.167C>G	p.Thr56Ser	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>G	p.Thr93Ser	missense	Exon 3 of 5	ENSP00000290855.6	Q9UHP7-1
	CLEC2D	ENST00000261340.11	TSL:1	c.278C>G	p.Thr93Ser	missense	Exon 3 of 6	ENSP00000261340.7	Q9UHP7-3
	CLEC2D	ENST00000430909.5	TSL:1	c.215C>G	p.Thr72Ser	missense	Exon 2 of 5	ENSP00000413045.1	A0A0C4DG81

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250254 AF XY: 0.00000739

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000822 AC: 12 AN: 1460494 Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5 AN XY: 726584

African (AFR) AF: 0.00 AC: 0 AN: 33364

American (AMR) AF: 0.00 AC: 0 AN: 44594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39456

South Asian (SAS) AF: 0.00 AC: 0 AN: 86142

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53384

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111378

Other (OTH) AF: 0.00 AC: 0 AN: 60308

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	5.8
DANN	Benign	0.78
DEOGEN2	Benign	0.031	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.51	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.39	N
PhyloP100		-0.29
PrimateAI	Benign	0.27	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.010
Sift	Benign	0.27	T
Sift4G	Benign	0.43	T
Polyphen		0.34	B
Vest4		0.12
MutPred		0.33		Gain of catalytic residue at S90 (P = 0)
MVP		0.043
MPC		0.12
ClinPred		0.053	T
GERP RS		-3.4
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.22
gMVP		0.14
Mutation Taster		=93/7	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.22		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.22		Position offset: 1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs757072519; hg19: chr12-9840603;