12-10435931-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002260.4(KLRC2):​c.56G>A​(p.Arg19Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000231 in 1,515,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R19P) has been classified as Benign.

Frequency

Genomes: 𝑓 0.000016 ( 0 hom., cov: 30)
Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

KLRC2
NM_002260.4 missense

Scores

3
13

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.132
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]

Genome browser will be placed here

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=0.093916).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KLRC2NM_002260.4 linkc.56G>A p.Arg19Gln missense_variant Exon 1 of 6 ENST00000381902.7 NP_002251.2 P26717

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KLRC2ENST00000381902.7 linkc.56G>A p.Arg19Gln missense_variant Exon 1 of 6 1 NM_002260.4 ENSP00000371327.2 P26717
ENSG00000255641ENST00000539033.1 linkc.56G>A p.Arg19Gln missense_variant Exon 1 of 7 1 ENSP00000437563.1 F5H6K3

Frequencies

GnomAD3 genomes
AF:
0.0000162
AC:
2
AN:
123470
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.0000588
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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
GnomAD4 exome
AF:
0.0000237
AC:
33
AN:
1392420
Hom.:
0
Cov.:
144
AF XY:
0.0000246
AC XY:
17
AN XY:
691698
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000284
Gnomad4 SAS exome
AF:
0.0000125
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000280
Gnomad4 OTH exome
AF:
0.0000178
GnomAD4 genome
AF:
0.0000162
AC:
2
AN:
123470
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
59920
show subpopulations
Gnomad4 AFR
AF:
0.0000588
Gnomad4 AMR
AF:
0.00
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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.098
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.66
CADD
Benign
12
DANN
Uncertain
1.0
Eigen
Benign
-0.75
Eigen_PC
Benign
-0.95
FATHMM_MKL
Benign
0.00048
N
LIST_S2
Benign
0.80
T;.;T
M_CAP
Benign
0.0019
T
MetaRNN
Benign
0.094
T;T;T
MetaSVM
Benign
-1.0
T
PROVEAN
Uncertain
-2.7
D;D;D
REVEL
Benign
0.013
Sift
Benign
0.11
T;D;T
Sift4G
Uncertain
0.043
D;D;D
Vest4
0.20
MutPred
0.36
Loss of MoRF binding (P = 0.0165);Loss of MoRF binding (P = 0.0165);Loss of MoRF binding (P = 0.0165);
MVP
0.061
MPC
1.3
ClinPred
0.24
T
GERP RS
-0.058
gMVP
0.058

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.

Other links and lift over

dbSNP: rs75545535; hg19: chr12-10588530; API