Variant 19-54852103-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_006737.4(KIR3DL2):c.176T>C(p.Met59Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,461,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 1 hom. )

Consequence

KIR3DL2
NM_006737.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -4.23

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033608496).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KIR3DL2	NM_006737.4 linkuse as main transcript	c.176T>C	p.Met59Thr	missense_variant	3/9	ENST00000326321.7
KIR3DL2	NM_001242867.2 linkuse as main transcript	c.176T>C	p.Met59Thr	missense_variant	3/8
KIR3DL2	XM_047438795.1 linkuse as main transcript	c.176T>C	p.Met59Thr	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KIR3DL2	ENST00000326321.7 linkuse as main transcript	c.176T>C	p.Met59Thr	missense_variant	3/9	1	NM_006737.4	P2	P43630-1
KIR3DL2	ENST00000270442.5 linkuse as main transcript	c.176T>C	p.Met59Thr	missense_variant	3/8	1		A2	P43630-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000238

AC:

AN:

168032

Hom.:

AF XY:

0.0000109

AC XY:

AN XY:

91808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000265

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461016

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

726842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000126

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

Bravo

AF:

0.0000113

ExAC

AF:

0.0000266

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.0020

DANN

Benign

0.21

DEOGEN2

Benign

0.012

T;.

Eigen

Benign

-2.6

Eigen_PC

Benign

-2.6

FATHMM_MKL

Benign

0.0011

M_CAP

Benign

0.00081

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.1

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.51

PROVEAN

Benign

1.5

N;N

REVEL

Benign

0.0070

Sift

Benign

1.0

T;T

Sift4G

Benign

0.45

T;T

Polyphen

0.0

B;.

Vest4

0.055

MVP

0.030

MPC

1.9

ClinPred

0.039

GERP RS

-3.2

Varity_R

0.044

gMVP

0.086

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over