rs759971718

Variant names:

• chr12-10432160-C-G
• rs759971718
• NM_002260.4:c.530G>C

Your query was ambiguous. Multiple possible variants found:

• chr12-10432160-C-G
• chr12-10432160-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_002260.4(KLRC2):​c.530G>C​(p.Arg177Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,382,386 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R177H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: KLRC2 NM_002260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC2	NM_002260.4	MANE Select	c.530G>C	p.Arg177Pro	missense	Exon 5 of 6	NP_002251.2	P26717

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRC2	ENST00000381902.7	TSL:1 MANE Select	c.530G>C	p.Arg177Pro	missense	Exon 5 of 6	ENSP00000371327.2	P26717
	ENSG00000255641	ENST00000539033.1	TSL:1	c.331+2326G>C		intron	N/A	ENSP00000437563.1	F5H6K3
	KLRC2	ENST00000381901.5	TSL:5	c.530G>C	p.Arg177Pro	missense	Exon 5 of 6	ENSP00000371326.1	J3KPJ4

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1382386 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 687922

African (AFR) AF: 0.00 AC: 0 AN: 30414

American (AMR) AF: 0.00 AC: 0 AN: 42940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24436

East Asian (EAS) AF: 0.00 AC: 0 AN: 36846

South Asian (SAS) AF: 0.00 AC: 0 AN: 80264

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50190

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5410

European-Non Finnish (NFE) AF: 9.48e-7 AC: 1 AN: 1055254

Other (OTH) AF: 0.00 AC: 0 AN: 56632

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.94
BayesDel_addAF	Benign	-0.051	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	21
DANN	Uncertain	0.98
Eigen	Benign	-0.49
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.021	N
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.0051	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.80	T
PhyloP100		0.19
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0050	D
Vest4		0.45
MutPred		0.62		Gain of catalytic residue at V175 (P = 0.0025)
MVP		0.40
MPC		1.2
ClinPred		0.96	D
GERP RS		0.48
gMVP		0.70
Mutation Taster		=85/15	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs759971718; hg19: chr12-10584759;