Variant 7-139483038-C-A 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_198508.4(KLRG2):c.605G>T(p.Arg202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,375,474 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: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 1 hom. )

Consequence

KLRG2
NM_198508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0830

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:

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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=0.04937896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLRG2	NM_198508.4 linkuse as main transcript	c.605G>T	p.Arg202Leu	missense_variant	1/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516140.3 linkuse as main transcript	c.605G>T	p.Arg202Leu	missense_variant	1/4		XP_011514442.1
KLRG2	XM_011516141.3 linkuse as main transcript	c.605G>T	p.Arg202Leu	missense_variant	1/4		XP_011514443.1
KLRG2	XM_005250311.4 linkuse as main transcript	c.605G>T	p.Arg202Leu	missense_variant	1/4		XP_005250368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG2	ENST00000340940.5 linkuse as main transcript	c.605G>T	p.Arg202Leu	missense_variant	1/5	1	NM_198508.4	ENSP00000339356	P1	A4D1S0-1
KLRG2	ENST00000393039.2 linkuse as main transcript	c.605G>T	p.Arg202Leu	missense_variant	1/2	5		ENSP00000376759		A4D1S0-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000620

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000368

AC:

AN:

1223242

Hom.:

Cov.:

AF XY:

0.0000573

AC XY:

AN XY:

593772

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000764

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.93e-7

Gnomad4 OTH exome

AF:

0.0000594

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152232

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000936

AC:

Asia WGS

AF:

0.000868

AC:

AN:

3472

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 28, 2023

The c.605G>T (p.R202L) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a G to T substitution at nucleotide position 605, causing the arginine (R) at amino acid position 202 to be replaced by a leucine (L). 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

0.13

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.57

CADD

Benign

7.3

DANN

Benign

0.94

DEOGEN2

Benign

0.0033

T;.

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.061

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0058

MetaRNN

Benign

0.049

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.90

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.59

PROVEAN

Benign

-0.86

N;N

REVEL

Benign

0.022

Sift

Benign

0.17

T;T

Sift4G

Benign

0.56

T;T

Polyphen

0.36

B;B

Vest4

0.089

MutPred

0.21

Gain of catalytic residue at R202 (P = 0.0579);Gain of catalytic residue at R202 (P = 0.0579);

MVP

0.11

MPC

1.1

ClinPred

0.12

GERP RS

1.1

Varity_R

0.046

gMVP

0.13

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