Variant chr7-139453694-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 ENST00000340940.5(KLRG2):c.1123G>A(p.Gly375Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000062 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

KLRG2
ENST00000340940.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.581

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=0.01764828).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLRG2	NM_198508.4 linkuse as main transcript	c.1123G>A	p.Gly375Ser	missense_variant	5/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_005250311.4 linkuse as main transcript	c.*5G>A		3_prime_UTR_variant	4/4		XP_005250368.1
KLRG2	XM_011516141.3 linkuse as main transcript	c.1005+25933G>A		intron_variant			XP_011514443.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG2	ENST00000340940.5 linkuse as main transcript	c.1123G>A	p.Gly375Ser	missense_variant	5/5	1	NM_198508.4	ENSP00000339356	P1	A4D1S0-1
KLRG2	ENST00000393039.2 linkuse as main transcript	c.771G>A	p.Thr257=	synonymous_variant	2/2	5		ENSP00000376759		A4D1S0-2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000845

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000844

AC:

AN:

248880

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

134734

show subpopulations

Gnomad AFR exome

AF:

0.000739

Gnomad AMR exome

AF:

0.000174

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000898

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000397

AC:

AN:

1461774

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727176

show subpopulations

Gnomad4 AFR exome

AF:

0.000836

Gnomad4 AMR exome

AF:

0.000201

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000135

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000276

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.000842

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000656

Hom.:

Bravo

AF:

0.000264

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000659

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 10, 2022

The c.1123G>A (p.G375S) alteration is located in exon 5 (coding exon 5) of the KLRG2 gene. This alteration results from a G to A substitution at nucleotide position 1123, causing the glycine (G) at amino acid position 375 to be replaced by a serine (S). 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

0.079

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.71

DEOGEN2

Benign

0.0023

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.43

M_CAP

Benign

0.0035

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.40

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.7

REVEL

Benign

0.037

Sift

Benign

0.41

Sift4G

Benign

0.48

Polyphen

0.11

Vest4

0.029

MVP

0.16

MPC

0.015

ClinPred

0.011

GERP RS

2.5

Varity_R

0.077

gMVP

0.39

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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