Variant 12-10435815-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_002260.4(KLRC2):c.172A>G(p.Ile58Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000106 in 1,548,652 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 3 hom., cov: 29)

Exomes 𝑓: 0.00010 ( 27 hom. )

Consequence

KLRC2
NM_002260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.931

Variant links:

Genes affected

KLRC2 (HGNC:6375): (killer cell lectin like receptor C2) Natural killer (NK) cells are lymphocytes that can mediate lysis of certain tumor cells and virus-infected cells without previous activation. They can also regulate specific humoral and cell-mediated immunity. NK cells preferentially express several calcium-dependent (C-type) lectins, which have been implicated in the regulation of NK cell function. The group, designated KLRC (NKG2) are expressed primarily in natural killer (NK) cells and encodes a family of transmembrane proteins characterized by a type II membrane orientation (extracellular C terminus) and the presence of a C-type lectin domain. The KLRC (NKG2) gene family is located within the NK complex, a region that contains several C-type lectin genes preferentially expressed on NK cells. KLRC2 alternative splice variants have been described but their full-length nature has not been determined. [provided by RefSeq, Jul 2008]

KLRC2 links:

ENSG00000255641 (HGNC:):

ENSG00000255641 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0196127).

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC2	NM_002260.4 linkuse as main transcript	c.172A>G	p.Ile58Val	missense_variant	1/6	ENST00000381902.7	NP_002251.2	P26717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC2	ENST00000381902.7 linkuse as main transcript	c.172A>G	p.Ile58Val	missense_variant	1/6	1	NM_002260.4	ENSP00000371327.2		P26717
ENSG00000255641	ENST00000539033.1 linkuse as main transcript	c.172A>G	p.Ile58Val	missense_variant	1/7	1		ENSP00000437563.1		F5H6K3

Frequencies

GnomAD3 genomes

AF:

0.000119

AC:

AN:

142262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000537

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000481

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:

0.000108

Gnomad OTH

AF:

0.000514

GnomAD3 exomes

AF:

0.000153

AC:

AN:

242140

Hom.:

AF XY:

0.000199

AC XY:

AN XY:

130914

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000352

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000174

Gnomad OTH exome

AF:

0.00102

GnomAD4 exome

AF:

0.000105

AC:

147

AN:

1406268

Hom.:

Cov.:

AF XY:

0.000110

AC XY:

AN XY:

700092

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000318

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:

0.0000972

Gnomad4 OTH exome

AF:

0.000433

GnomAD4 genome

AF:

0.000119

AC:

AN:

142384

Hom.:

Cov.:

AF XY:

0.000101

AC XY:

AN XY:

69396

show subpopulations

Gnomad4 AFR

AF:

0.0000535

Gnomad4 AMR

AF:

0.000481

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000108

Gnomad4 OTH

AF:

0.000509

Alfa

AF:

0.000193

Hom.:

ExAC

AF:

0.000127

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

Aug 12, 2021

The c.172A>G (p.I58V) alteration is located in exon 1 (coding exon 1) of the KLRC2 gene. This alteration results from a A to G substitution at nucleotide position 172, causing the isoleucine (I) at amino acid position 58 to be replaced by a valine (V). 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

0.089

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.7

DANN

Benign

0.54

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0044

LIST_S2

Benign

0.60

T;.;T

M_CAP

Benign

0.0012

MetaRNN

Benign

0.020

T;T;T

MetaSVM

Benign

-0.96

PROVEAN

Benign

0.23

N;N;N

REVEL

Benign

0.015

Sift

Benign

0.50

T;T;T

Sift4G

Benign

0.17

T;T;T

Vest4

0.20

MVP

0.048

MPC

0.38

ClinPred

0.043

GERP RS

0.61

gMVP

0.039

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