NM_002260.4:c.20C>A

Variant names:

• chr12-10435967-G-T
• rs149277235
• NM_002260.4:c.20C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002260.4(KLRC2):​c.20C>A​(p.Thr7Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,102 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. T7I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KLRC2 NM_002260.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.27
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12433198).

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.20C>A	p.Thr7Asn	missense	Exon 1 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.20C>A	p.Thr7Asn	missense	Exon 1 of 6	ENSP00000371327.2	P26717
	ENSG00000255641	ENST00000539033.1	TSL:1	c.20C>A	p.Thr7Asn	missense	Exon 1 of 7	ENSP00000437563.1	F5H6K3
	KLRC2	ENST00000381901.5	TSL:5	c.20C>A	p.Thr7Asn	missense	Exon 1 of 6	ENSP00000371326.1	J3KPJ4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458102 Hom.: 0 Cov.: 138 AF XY: 0.00 AC XY: 0 AN XY: 725396

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33206

American (AMR) AF: 0.00 AC: 0 AN: 44588

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25998

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.00 AC: 0 AN: 86096

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53248

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5742

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109668

Other (OTH) AF: 0.00 AC: 0 AN: 60122

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.085
DANN	Benign	0.92
Eigen	Benign	-0.76
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.00055	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0010	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
PhyloP100		-4.3
PROVEAN	Uncertain	-3.0	D
REVEL	Benign	0.032
Sift	Benign	0.053	T
Sift4G	Benign	0.080	T
Vest4		0.088
MutPred		0.26		Gain of sheet (P = 0.0085)
MVP		0.030
MPC		0.83
ClinPred		0.29	T
GERP RS		-2.2
PromoterAI		-0.021	Neutral
gMVP		0.089
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs149277235; hg19: chr12-10588566;