rs28403159

Variant names:

• chr12-10435982-T-C
• rs28403159
• NM_002260.4:c.5A>G

Your query was ambiguous. Multiple possible variants found:

• chr12-10435982-T-C
• chr12-10435982-T-A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BP6_Very_Strong

The NM_002260.4(KLRC2):​c.5A>G​(p.Asn2Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.39 (453 hom., cov: 32)
  • Exomes 𝑓: 0.43 (3217 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRC2 NM_002260.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0290
• Publications: 24 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0028169751).
• BP6: Variant 12-10435982-T-C is Benign according to our data. Variant chr12-10435982-T-C is described in ClinVar as Benign. ClinVar VariationId is 769387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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.5A>G	p.Asn2Ser	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.5A>G	p.Asn2Ser	missense	Exon 1 of 6	ENSP00000371327.2	P26717
	ENSG00000255641	ENST00000539033.1	TSL:1	c.5A>G	p.Asn2Ser	missense	Exon 1 of 7	ENSP00000437563.1	F5H6K3
	KLRC2	ENST00000381901.5	TSL:5	c.5A>G	p.Asn2Ser	missense	Exon 1 of 6	ENSP00000371326.1	J3KPJ4

Frequencies

GnomAD3 genomes AF: 0.391 AC: 57073 AN: 145900 Hom.: 455 Cov.: 32

Gnomad AFR AF: 0.243

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.424

Gnomad SAS AF: 0.402

Gnomad FIN AF: 0.453

Gnomad MID AF: 0.410

Gnomad NFE AF: 0.454

Gnomad OTH AF: 0.413

GnomAD2 exomes AF: 0.401 AC: 87448 AN: 217968 AF XY: 0.404

Gnomad AFR exome AF: 0.171

Gnomad AMR exome AF: 0.419

Gnomad ASJ exome AF: 0.411

Gnomad EAS exome AF: 0.373

Gnomad FIN exome AF: 0.426

Gnomad NFE exome AF: 0.430

Gnomad OTH exome AF: 0.424

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.429 AC: 545118 AN: 1269826 Hom.: 3217 Cov.: 110 AF XY: 0.429 AC XY: 272633 AN XY: 635372

African (AFR) AF: 0.188 AC: 5522 AN: 29314

American (AMR) AF: 0.428 AC: 17337 AN: 40492

Ashkenazi Jewish (ASJ) AF: 0.415 AC: 10056 AN: 24252

East Asian (EAS) AF: 0.410 AC: 15154 AN: 36960

South Asian (SAS) AF: 0.391 AC: 30383 AN: 77736

European-Finnish (FIN) AF: 0.438 AC: 21791 AN: 49708

Middle Eastern (MID) AF: 0.409 AC: 2085 AN: 5096

European-Non Finnish (NFE) AF: 0.441 AC: 420753 AN: 953328

Other (OTH) AF: 0.416 AC: 22037 AN: 52940

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff AF: 0.391 AC: 57094 AN: 146024 Hom.: 453 Cov.: 32 AF XY: 0.391 AC XY: 27881 AN XY: 71218

African (AFR) AF: 0.242 AC: 9576 AN: 39526

American (AMR) AF: 0.441 AC: 6446 AN: 14612

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1413 AN: 3378

East Asian (EAS) AF: 0.424 AC: 2027 AN: 4778

South Asian (SAS) AF: 0.401 AC: 1855 AN: 4622

European-Finnish (FIN) AF: 0.453 AC: 4505 AN: 9950

Middle Eastern (MID) AF: 0.411 AC: 111 AN: 270

European-Non Finnish (NFE) AF: 0.454 AC: 29954 AN: 66038

Other (OTH) AF: 0.414 AC: 819 AN: 1980

Alfa AF: 0.362 Hom.: 47

ExAC AF: 0.393 AC: 47741

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.078
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.0
DANN	Benign	0.82
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00068	N
LIST_S2	Benign	0.67	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.87	T
PhyloP100		0.029
PROVEAN	Uncertain	-2.6	D
REVEL	Benign	0.013
Sift	Benign	0.34	T
Sift4G	Benign	0.15	T
Vest4		0.058
MPC		0.37
ClinPred		0.0067	T
GERP RS		-0.46
PromoterAI		0.023	Neutral
gMVP		0.049
Mutation Taster		=98/2	polymorphism (auto)

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: rs28403159; hg19: chr12-10588581; COSMIC: COSV67899388; COSMIC: COSV67899388;