12-10433880-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_002260.4(KLRC2):c.394G>A(p.Gly132Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,550,410 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00015 ( 5 hom., cov: 27)

Exomes 𝑓: 0.000012 ( 3 hom. )

Consequence

KLRC2
NM_002260.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.775

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 12-10433880-C-T is Benign according to our data. Variant chr12-10433880-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3115918.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC2	NM_002260.4 link	c.394G>A	p.Gly132Ser	missense_variant	Exon 4 of 6	ENST00000381902.7	NP_002251.2	P26717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC2	ENST00000381902.7 link	c.394G>A	p.Gly132Ser	missense_variant	Exon 4 of 6	1	NM_002260.4	ENSP00000371327.2		P26717
ENSG00000255641	ENST00000539033.1 link	c.331+606G>A		intron_variant	Intron 3 of 6	1		ENSP00000437563.1		F5H6K3

Frequencies

GnomAD3 genomes

AF:

0.000148

AC:

AN:

141882

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000691

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000454

AC:

AN:

242186

Hom.:

AF XY:

0.0000534

AC XY:

AN XY:

130968

show subpopulations

Gnomad AFR exome

AF:

0.000729

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:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000121

AC:

AN:

1408528

Hom.:

Cov.:

AF XY:

0.0000128

AC XY:

AN XY:

701126

show subpopulations

Gnomad4 AFR exome

AF:

0.000513

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:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

AF:

0.000148

AC:

AN:

141882

Hom.:

Cov.:

AF XY:

0.000159

AC XY:

AN XY:

69084

show subpopulations

Gnomad4 AFR

AF:

0.000538

Gnomad4 AMR

AF:

0.0000691

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000845

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Oct 24, 2023

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.63

CADD

Benign

6.4

DANN

Benign

0.63

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0010

LIST_S2

Benign

0.84

.;T;T;D

M_CAP

Benign

0.00094

MetaRNN

Benign

0.029

T;T;T;T

MetaSVM

Benign

-0.97

PROVEAN

Benign

-0.20

N;.;N;N

REVEL

Benign

0.10

Sift

Benign

0.98

T;.;T;T

Sift4G

Benign

1.0

T;T;T;T

Vest4

0.22

MVP

0.095

MPC

0.34

ClinPred

0.070

GERP RS

-5.3

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.42

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.42

Position offset: -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