Variant 7-139483540-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198508.4(KLRG2):c.103C>A(p.Pro35Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,598,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

KLRG2
NM_198508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

Variant links:

Genes affected

KLRG2 (HGNC:24778): (killer cell lectin like receptor G2) Predicted to enable carbohydrate binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

KLRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.17690545).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
KLRG2	NM_198508.4 linkuse as main transcript	c.103C>A	p.Pro35Thr	missense_variant	1/5	ENST00000340940.5
KLRG2	XM_011516140.3 linkuse as main transcript	c.103C>A	p.Pro35Thr	missense_variant	1/4
KLRG2	XM_011516141.3 linkuse as main transcript	c.103C>A	p.Pro35Thr	missense_variant	1/4
KLRG2	XM_005250311.4 linkuse as main transcript	c.103C>A	p.Pro35Thr	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRG2	ENST00000340940.5 linkuse as main transcript	c.103C>A	p.Pro35Thr	missense_variant	1/5	1	NM_198508.4	P1	A4D1S0-1
KLRG2	ENST00000393039.2 linkuse as main transcript	c.103C>A	p.Pro35Thr	missense_variant	1/2	5			A4D1S0-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000448

AC:

AN:

223336

Hom.:

AF XY:

0.0000563

AC XY:

AN XY:

124338

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000989

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000116

AC:

168

AN:

1446426

Hom.:

Cov.:

AF XY:

0.000111

AC XY:

AN XY:

720078

show subpopulations

Gnomad4 AFR exome

AF:

0.0000606

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000146

Gnomad4 OTH exome

AF:

0.0000665

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152196

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000965

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000894

Hom.:

Bravo

AF:

0.0000604

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000338

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000595

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 13, 2023

The c.103C>A (p.P35T) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a C to A substitution at nucleotide position 103, causing the proline (P) at amino acid position 35 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.46

Cadd

Benign

Dann

Uncertain

0.99

DEOGEN2

Benign

0.0063

T;.

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.18

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.4

N;D

REVEL

Benign

0.063

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.21

T;D

Polyphen

1.0

D;D

Vest4

0.082

MVP

0.36

MPC

1.1

ClinPred

0.18

GERP RS

3.2

Varity_R

0.085

gMVP

0.19

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over