Variant 7-139453669-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_198508.4(KLRG2):c.1148G>A(p.Cys383Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000123 in 1,461,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

KLRG2
NM_198508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16

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_pathogenic. Variant got 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.974

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLRG2	NM_198508.4 linkuse as main transcript	c.1148G>A	p.Cys383Tyr	missense_variant	5/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_005250311.4 linkuse as main transcript	c.*30G>A		3_prime_UTR_variant	4/4		XP_005250368.1
KLRG2	XM_011516141.3 linkuse as main transcript	c.1005+25958G>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.1148G>A	p.Cys383Tyr	missense_variant	5/5	1	NM_198508.4	ENSP00000339356	P1	A4D1S0-1
KLRG2	ENST00000393039.2 linkuse as main transcript	c.796G>A	p.Val266Met	missense_variant	2/2	5		ENSP00000376759		A4D1S0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000802

AC:

AN:

249260

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134908

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

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:

0.0000123

AC:

AN:

1461786

Hom.:

Cov.:

AF XY:

0.0000151

AC XY:

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.000232

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000480

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

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

Nov 28, 2023

The c.1148G>A (p.C383Y) 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 1148, causing the cysteine (C) at amino acid position 383 to be replaced by a tyrosine (Y). 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

0.96

BayesDel_addAF

Pathogenic

0.17

BayesDel_noAF

Pathogenic

0.17

CADD

Uncertain

DANN

Benign

0.58

DEOGEN2

Benign

0.14

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.051

FATHMM_MKL

Benign

0.33

LIST_S2

Benign

0.43

M_CAP

Benign

0.038

MetaRNN

Pathogenic

0.97

MetaSVM

Benign

-0.66

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

0.99

N;N

PrimateAI

Uncertain

0.49

PROVEAN

Pathogenic

-9.2

REVEL

Uncertain

0.42

Sift

Uncertain

0.012

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.84

MutPred

0.85

Gain of catalytic residue at C383 (P = 0.0328);

MVP

0.49

MPC

0.12

ClinPred

0.99

GERP RS

4.9

Varity_R

0.91

gMVP

0.95

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