NM_006737.4:c.1190C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_006737.4(KIR3DL2):c.1190C>T(p.Thr397Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,613,670 control chromosomes in the GnomAD database, including 77,085 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 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: 𝑓 0.27 ( 6010 hom., cov: 31)

Exomes 𝑓: 0.31 ( 71075 hom. )

Consequence

KIR3DL2
NM_006737.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.309

Publications

38 publications found

Variant links:

Genes affected

KIR3DL2 (HGNC:6339): (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 2) 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. This gene is one of the "framework" loci that is present on all haplotypes. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Jun 2011]

KIR3DL2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0060640574).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.371 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KIR3DL2	NM_006737.4 link	c.1190C>T	p.Thr397Met	missense_variant	Exon 9 of 9	ENST00000326321.7	NP_006728.2	P43630-1A0A0U1WNF3Q8NHK6
KIR3DL2	NM_001242867.2 link	c.1139C>T	p.Thr380Met	missense_variant	Exon 8 of 8		NP_001229796.1	P43630-2Q8NHI6
KIR3DL2	XM_047438795.1 link	c.1034C>T	p.Thr345Met	missense_variant	Exon 7 of 7		XP_047294751.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KIR3DL2	ENST00000326321.7 link	c.1190C>T	p.Thr397Met	missense_variant	Exon 9 of 9	1	NM_006737.4	ENSP00000325525.3		P43630-1
KIR3DL2	ENST00000270442.6 link	c.1139C>T	p.Thr380Met	missense_variant	Exon 8 of 8	1		ENSP00000270442.5		P43630-2

Frequencies

GnomAD3 genomes

AF:

0.265

AC:

40294

AN:

151806

Hom.:

5997

Cov.:

show subpopulations

Gnomad AFR

AF:

0.132

Gnomad AMI

AF:

0.260

Gnomad AMR

AF:

0.344

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.282

Gnomad SAS

AF:

0.385

Gnomad FIN

AF:

0.329

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.283

GnomAD2 exomes

AF:

0.316

AC:

79475

AN:

251458

AF XY:

0.322

show subpopulations

Gnomad AFR exome

AF:

0.127

Gnomad AMR exome

AF:

0.370

Gnomad ASJ exome

AF:

0.346

Gnomad EAS exome

AF:

0.283

Gnomad FIN exome

AF:

0.330

Gnomad NFE exome

AF:

0.307

Gnomad OTH exome

AF:

0.325

GnomAD4 exome

AF:

0.306

AC:

447281

AN:

1461746

Hom.:

71075

Cov.:

AF XY:

0.309

AC XY:

224785

AN XY:

727172

show subpopulations

African (AFR)

AF:

0.124

AC:

4163

AN:

33478

American (AMR)

AF:

0.367

AC:

16411

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.344

AC:

8981

AN:

26136

East Asian (EAS)

AF:

0.289

AC:

11466

AN:

39700

South Asian (SAS)

AF:

0.384

AC:

33111

AN:

86254

European-Finnish (FIN)

AF:

0.336

AC:

17931

AN:

53384

Middle Eastern (MID)

AF:

0.270

AC:

1556

AN:

5768

European-Non Finnish (NFE)

AF:

0.301

AC:

334913

AN:

1111910

Other (OTH)

AF:

0.310

AC:

18749

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

Heterozygous variant carriers

22956

45913

68869

91826

114782

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10992

21984

32976

43968

54960

<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:

0.265

AC:

40318

AN:

151924

Hom.:

6010

Cov.:

AF XY:

0.272

AC XY:

20199

AN XY:

74236

show subpopulations

African (AFR)

AF:

0.131

AC:

5450

AN:

41484

American (AMR)

AF:

0.344

AC:

5263

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1205

AN:

3466

East Asian (EAS)

AF:

0.282

AC:

1460

AN:

5172

South Asian (SAS)

AF:

0.386

AC:

1858

AN:

4814

European-Finnish (FIN)

AF:

0.329

AC:

3456

AN:

10490

Middle Eastern (MID)

AF:

0.190

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.305

AC:

20723

AN:

67908

Other (OTH)

AF:

0.290

AC:

611

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1484

2968

4451

5935

7419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

414

828

1242

1656

2070

<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:

0.284

Hom.:

8342

Bravo

AF:

0.257

TwinsUK

AF:

0.303

AC:

1123

ALSPAC

AF:

0.305

AC:

1177

ESP6500AA

AF:

0.137

AC:

602

ESP6500EA

AF:

0.295

AC:

2541

ExAC

AF:

0.311

AC:

37801

Asia WGS

AF:

0.373

AC:

1300

AN:

3478

EpiCase

AF:

0.310

EpiControl

AF:

0.311

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.67

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.14

T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.0053

MetaRNN

Benign

0.0061

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Pathogenic

3.4

M;.

PhyloP100

-0.31

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.051

Sift

Uncertain

0.017

D;D

Sift4G

Uncertain

0.054

T;T

Polyphen

0.99

D;.

Vest4

0.066

MPC

0.0068

ClinPred

0.054

GERP RS

0.46

Varity_R

0.043

gMVP

0.21

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over