Variant 7-139483131-A-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.512T>A(p.Leu171His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000045 in 1,332,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000045 ( 0 hom. )

Consequence

KLRG2
NM_198508.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.503

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 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=0.15513295).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
KLRG2	NM_198508.4 linkuse as main transcript	c.512T>A	p.Leu171His	missense_variant	1/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516140.3 linkuse as main transcript	c.512T>A	p.Leu171His	missense_variant	1/4		XP_011514442.1
KLRG2	XM_011516141.3 linkuse as main transcript	c.512T>A	p.Leu171His	missense_variant	1/4		XP_011514443.1
KLRG2	XM_005250311.4 linkuse as main transcript	c.512T>A	p.Leu171His	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.512T>A	p.Leu171His	missense_variant	1/5	1	NM_198508.4	ENSP00000339356	P1	A4D1S0-1
KLRG2	ENST00000393039.2 linkuse as main transcript	c.512T>A	p.Leu171His	missense_variant	1/2	5		ENSP00000376759		A4D1S0-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000450

AC:

AN:

1332912

Hom.:

Cov.:

AF XY:

0.00000609

AC XY:

AN XY:

656936

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000567

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 06, 2022

The c.512T>A (p.L171H) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a T to A substitution at nucleotide position 512, causing the leucine (L) at amino acid position 171 to be replaced by a histidine (H). 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

0.11

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.64

DEOGEN2

Benign

0.0090

T;.

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.36

T;T

M_CAP

Benign

0.033

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.81

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.058

Sift

Uncertain

0.025

D;T

Sift4G

Benign

0.13

T;T

Polyphen

1.0

D;D

Vest4

0.18

MutPred

0.30

Loss of MoRF binding (P = 0.1434);Loss of MoRF binding (P = 0.1434);

MVP

0.18

MPC

1.8

ClinPred

0.31

GERP RS

-0.97

Varity_R

0.062

gMVP

0.15

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over