12-10435931-C-T

Variant names:

• chr12-10435931-C-T
• rs75545535
• NM_002260.4:c.56G>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.132

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]

ENSG00000255641 (HGNC:):

ACMG classification

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
KLRC2	NM_002260.4	c.56G>A	p.Arg19Gln	missense_variant	Exon 1 of 6	ENST00000381902.7	NP_002251.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC2	ENST00000381902.7	c.56G>A	p.Arg19Gln	missense_variant	Exon 1 of 6	1	NM_002260.4	ENSP00000371327.2
ENSG00000255641	ENST00000539033.1	c.56G>A	p.Arg19Gln	missense_variant	Exon 1 of 7	1		ENSP00000437563.1

Frequencies

GnomAD3 genomes AF: 0.0000162 AC: 2 AN: 123470 Hom.: 0 Cov.: 30

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

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

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

Other links and lift over

dbSNP: rs75545535; hg19: chr12-10588530;