dbSNP rs10772256: KLRD1:p.Ser25Thr (chr12-10309453-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002262.5(KLRD1):c.73T>A(p.Ser25Thr) 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. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLRD1
NM_002262.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.110

Publications

28 publications found

Variant links:

Genes affected

KLRD1 (HGNC:6378): (killer cell lectin like receptor D1) Natural killer (NK) cells are a distinct lineage of lymphocytes that mediate cytotoxic activity and secrete cytokines upon immune stimulation. Several genes of the C-type lectin superfamily, including members of the NKG2 family, are expressed by NK cells and may be involved in the regulation of NK cell function. KLRD1 (CD94) is an antigen preferentially expressed on NK cells and is classified as a type II membrane protein because it has an external C terminus. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2017]

KLRD1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.061225712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRD1	NM_002262.5 link	c.73T>A	p.Ser25Thr	missense_variant	Exon 2 of 6	ENST00000336164.9	NP_002253.2	Q13241-1Q53ZY6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRD1	ENST00000336164.9 link	c.73T>A	p.Ser25Thr	missense_variant	Exon 2 of 6	1	NM_002262.5	ENSP00000338130.4		Q13241-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1386910

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

694834

African (AFR)

AF:

0.00

AC:

AN:

32144

American (AMR)

AF:

0.00

AC:

AN:

44642

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25672

East Asian (EAS)

AF:

0.00

AC:

AN:

39304

South Asian (SAS)

AF:

0.00

AC:

AN:

84706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5628

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043624

Other (OTH)

AF:

0.00

AC:

AN:

57804

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.71

CADD

Benign

1.0

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.085

T;T;.;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0067

LIST_S2

Benign

0.025

.;T;.;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.38

N;N;.;.

PhyloP100

-0.11

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.36

N;N;N;N

REVEL

Benign

0.015

Sift

Benign

0.048

D;D;D;T

Sift4G

Benign

0.41

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.095

MutPred

0.50

Gain of catalytic residue at S22 (P = 0);Gain of catalytic residue at S22 (P = 0);Gain of catalytic residue at S22 (P = 0);Gain of catalytic residue at S22 (P = 0);

MVP

0.16

MPC

0.13

ClinPred

0.057

GERP RS

-3.8

Varity_R

0.045

gMVP

0.22

Mutation Taster

=99/1

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over