dbSNP rs3764021: CLEC2D:p.Ser57Arg (chr12-9681032-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013269.6(CLEC2D):c.171C>A(p.Ser57Arg) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000757 in 1,321,774 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

CLEC2D
NM_013269.6 missense, splice_region

Scores

Splicing: ADA: 0.00003056

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.588

Publications

0 publications found

Variant links:

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]

CLEC2D links:

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ACMG classification

Classification was made for transcript

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=0.11700669).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLEC2D	NM_013269.6 link	c.171C>A	p.Ser57Arg	missense_variant, splice_region_variant	Exon 2 of 5	ENST00000290855.11	NP_037401.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLEC2D	ENST00000290855.11 link	c.171C>A	p.Ser57Arg	missense_variant, splice_region_variant	Exon 2 of 5	1	NM_013269.6	ENSP00000290855.6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.57e-7

AC:

AN:

1321774

Hom.:

Cov.:

AF XY:

0.00000150

AC XY:

AN XY:

664610

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

30502

American (AMR)

AF:

0.00

AC:

AN:

44118

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25102

East Asian (EAS)

AF:

0.00

AC:

AN:

38982

South Asian (SAS)

AF:

0.00

AC:

AN:

82754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51852

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5498

European-Non Finnish (NFE)

AF:

0.00000101

AC:

AN:

987328

Other (OTH)

AF:

0.00

AC:

AN:

55638

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

0.035

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0097

.;T;.;T;.

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.0015

LIST_S2

Benign

0.63

T;T;T;T;T

M_CAP

Benign

0.0017

MetaRNN

Benign

0.12

T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

L;L;L;.;.

PhyloP100

-0.59

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-2.4

N;N;N;N;N

REVEL

Benign

0.12

Sift

Benign

0.34

T;T;T;T;T

Sift4G

Benign

0.43

T;T;T;T;T

Polyphen

1.0

D;P;D;.;.

Vest4

0.19

MutPred

0.59

Gain of catalytic residue at M52 (P = 0);Gain of catalytic residue at M52 (P = 0);Gain of catalytic residue at M52 (P = 0);.;.;

MVP

0.068

MPC

0.11

ClinPred

0.61

GERP RS

-2.4

PromoterAI

0.00040

Neutral

(source)

Varity_R

0.044

gMVP

0.29

Mutation Taster

=88/12

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.16

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over