Variant 7-139483261-C-T 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.382G>A(p.Val128Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000254 in 1,559,856 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00026 ( 1 hom. )

Consequence

KLRG2
NM_198508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.54

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 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=0.047892928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLRG2	NM_198508.4 linkuse as main transcript	c.382G>A	p.Val128Met	missense_variant	1/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516140.3 linkuse as main transcript	c.382G>A	p.Val128Met	missense_variant	1/4		XP_011514442.1
KLRG2	XM_011516141.3 linkuse as main transcript	c.382G>A	p.Val128Met	missense_variant	1/4		XP_011514443.1
KLRG2	XM_005250311.4 linkuse as main transcript	c.382G>A	p.Val128Met	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.382G>A	p.Val128Met	missense_variant	1/5	1	NM_198508.4	ENSP00000339356	P1	A4D1S0-1
KLRG2	ENST00000393039.2 linkuse as main transcript	c.382G>A	p.Val128Met	missense_variant	1/2	5		ENSP00000376759		A4D1S0-2

Frequencies

GnomAD3 genomes

AF:

0.000204

AC:

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000203

AC:

AN:

167834

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

95168

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:

0.000695

Gnomad NFE exome

AF:

0.000332

Gnomad OTH exome

AF:

0.000720

GnomAD4 exome

AF:

0.000259

AC:

365

AN:

1407746

Hom.:

Cov.:

AF XY:

0.000243

AC XY:

170

AN XY:

699252

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.0000405

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00126

Gnomad4 NFE exome

AF:

0.000276

Gnomad4 OTH exome

AF:

0.000256

GnomAD4 genome

AF:

0.000204

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74306

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000268

Hom.:

Bravo

AF:

0.000147

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000249

AC:

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

Jan 26, 2023

The c.382G>A (p.V128M) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a G to A substitution at nucleotide position 382, causing the valine (V) at amino acid position 128 to be replaced by a methionine (M). 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

Pathogenic

0.63

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0047

T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.17

FATHMM_MKL

Benign

0.71

LIST_S2

Benign

0.71

T;T

M_CAP

Benign

0.061

MetaRNN

Benign

0.048

T;T

MetaSVM

Benign

-0.80

MutationAssessor

Benign

0.97

L;L

MutationTaster

Benign

0.93

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.10

Sift

Pathogenic

0.0

D;D

Sift4G

Benign

0.12

T;T

Polyphen

1.0

D;D

Vest4

0.19

MutPred

0.20

Gain of MoRF binding (P = 0.1143);Gain of MoRF binding (P = 0.1143);

MVP

0.47

MPC

1.9

ClinPred

0.14

GERP RS

3.5

Varity_R

0.30

gMVP

0.13

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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