Genetic Variant KIR2DL1:p.Val5Leu (chr19-54769863-G-C) – 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_014218.3(KIR2DL1):c.13G>C(p.Val5Leu) 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. 15/20 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: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KIR2DL1
NM_014218.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.885

Publications

15 publications found

Variant links:

Genes affected

KIR2DL1 (HGNC:6329): (killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 1) Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]

KIR2DL1 links:

LOC101928804 (HGNC:):

LOC101928804 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=0.09625727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIR2DL1	NM_014218.3 link	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 8	ENST00000336077.11	NP_055033.2	P43626Q6H2H3Q6H2H2
LOC101928804	NR_110737.1 link	n.340C>G		non_coding_transcript_exon_variant	Exon 3 of 3
LOC101928804	NR_110738.1 link	n.269C>G		non_coding_transcript_exon_variant	Exon 3 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIR2DL1	ENST00000336077.11 link	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 8	1	NM_014218.3	ENSP00000336769.5	Q6H2H3
KIR2DL1	ENST00000291633.7 link	c.13G>C	p.Val5Leu	missense_variant	Exon 1 of 9	1		ENSP00000291633.7	P43626
ENSG00000215765	ENST00000400864.3 link	n.36-986G>C		intron_variant	Intron 1 of 5	5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1414094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

703942

African (AFR)

AF:

0.00

AC:

AN:

32928

American (AMR)

AF:

0.00

AC:

AN:

43516

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24678

East Asian (EAS)

AF:

0.00

AC:

AN:

39458

South Asian (SAS)

AF:

0.00

AC:

AN:

84548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1073824

Other (OTH)

AF:

0.00

AC:

AN:

58496

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

973

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

6.2

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0063

M_CAP

Benign

0.0057

MetaRNN

Benign

0.096

T;T

MetaSVM

Benign

-0.92

PhyloP100

-0.89

PrimateAI

Benign

0.47

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.043

Sift

Uncertain

0.0030

D;D

Sift4G

Benign

0.63

T;T

Polyphen

0.082

B;.

Vest4

0.16

MutPred

0.39

Loss of catalytic residue at V5 (P = 0.007);Loss of catalytic residue at V5 (P = 0.007);

MVP

0.15

MPC

0.97

ClinPred

0.099

GERP RS

-1.0

PromoterAI

0.033

Neutral

(source)

gMVP

0.084

Mutation Taster

=97/3

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