rs371289444

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_014218.3(KIR2DL1):c.107G>A(p.Gly36Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0049 in 1,598,146 control chromosomes in the GnomAD database, including 271 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0034 ( 47 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 224 hom. )

Consequence

KIR2DL1
NM_014218.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.156

Publications

3 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:

ENSG00000215765 (HGNC:):

ENSG00000215765 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012991875).

BP6

Variant 19-54773369-G-A is Benign according to our data. Variant chr19-54773369-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2650462.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 47 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIR2DL1	NM_014218.3 link	c.107G>A	p.Gly36Asp	missense_variant	Exon 3 of 8	ENST00000336077.11	NP_055033.2	P43626Q6H2H3Q6H2H2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
KIR2DL1	ENST00000336077.11 link	c.107G>A	p.Gly36Asp	missense_variant	Exon 3 of 8	1	NM_014218.3	ENSP00000336769.5	Q6H2H3
KIR2DL1	ENST00000291633.7 link	c.107G>A	p.Gly36Asp	missense_variant	Exon 3 of 9	1		ENSP00000291633.7	P43626
ENSG00000215765	ENST00000400864.3 link	n.71+2485G>A		intron_variant	Intron 2 of 5	5

Frequencies

GnomAD3 genomes

AF:

0.00342

AC:

507

AN:

148324

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000545

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00405

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00612

Gnomad OTH

AF:

0.00196

GnomAD2 exomes

AF:

0.00137

AC:

259

AN:

189592

AF XY:

0.00121

show subpopulations

Gnomad AFR exome

AF:

0.000454

Gnomad AMR exome

AF:

0.000231

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00148

Gnomad NFE exome

AF:

0.00265

Gnomad OTH exome

AF:

0.00240

GnomAD4 exome

AF:

0.00505

AC:

7323

AN:

1449702

Hom.:

224

Cov.:

AF XY:

0.00482

AC XY:

3478

AN XY:

721206

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

33284

American (AMR)

AF:

0.000407

AC:

AN:

44276

Ashkenazi Jewish (ASJ)

AF:

0.000273

AC:

AN:

25644

East Asian (EAS)

AF:

0.00

AC:

AN:

39492

South Asian (SAS)

AF:

0.0000815

AC:

AN:

85842

European-Finnish (FIN)

AF:

0.00479

AC:

252

AN:

52610

Middle Eastern (MID)

AF:

0.000178

AC:

AN:

5618

European-Non Finnish (NFE)

AF:

0.00609

AC:

6722

AN:

1103276

Other (OTH)

AF:

0.00473

AC:

282

AN:

59660

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.406

Heterozygous variant carriers

213

425

638

850

1063

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

248

496

744

992

1240

<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

AF:

0.00342

AC:

507

AN:

148444

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

235

AN XY:

72464

show subpopulations

African (AFR)

AF:

0.00115

AC:

AN:

40710

American (AMR)

AF:

0.000544

AC:

AN:

14708

Ashkenazi Jewish (ASJ)

AF:

0.000293

AC:

AN:

3408

East Asian (EAS)

AF:

0.00

AC:

AN:

5136

South Asian (SAS)

AF:

0.00

AC:

AN:

4708

European-Finnish (FIN)

AF:

0.00405

AC:

AN:

10380

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.00612

AC:

405

AN:

66154

Other (OTH)

AF:

0.00194

AC:

AN:

2062

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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

Alfa

AF:

0.00418

Hom.:

ESP6500AA

AF:

0.000499

AC:

ESP6500EA

AF:

0.000805

AC:

ExAC

AF:

0.00109

AC:

123

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Oct 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KIR2DL1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.23

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.028

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.84

FATHMM_MKL

Benign

0.0033

M_CAP

Benign

0.0013

MetaRNN

Benign

0.013

T;T

MetaSVM

Benign

-1.0

PhyloP100

-0.16

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-3.6

D;D

REVEL

Benign

0.065

Sift

Uncertain

0.0040

D;D

Sift4G

Uncertain

0.029

D;T

Polyphen

0.99

D;.

Vest4

0.16

MVP

0.45

MPC

1.2

ClinPred

0.079

GERP RS

-1.8

gMVP

0.15

Mutation Taster

=100/0

polymorphism (auto)

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over