Genetic Variant NM_002260.4:c.20C>T (chr12-10435967-G-A) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_002260.4(KLRC2):c.20C>T(p.Thr7Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,605,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00041 ( 0 hom. )

Consequence

KLRC2
NM_002260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.27

Publications

1 publications found

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]

KLRC2 links:

ENSG00000255641 (HGNC:):

ENSG00000255641 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013810486).

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>T	p.Thr7Ile	missense	Exon 1 of 6	NP_002251.2	P26717

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
KLRC2	ENST00000381902.7	TSL:1 MANE Select	c.20C>T	p.Thr7Ile	missense	Exon 1 of 6	ENSP00000371327.2	P26717
ENSG00000255641	ENST00000539033.1	TSL:1	c.20C>T	p.Thr7Ile	missense	Exon 1 of 7	ENSP00000437563.1	F5H6K3
KLRC2	ENST00000381901.5	TSL:5	c.20C>T	p.Thr7Ile	missense	Exon 1 of 6	ENSP00000371326.1	J3KPJ4

Frequencies

GnomAD3 genomes

AF:

0.000155

AC:

AN:

148516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000251

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:

0.000328

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000408

AC:

102

AN:

250192

AF XY:

0.000451

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000232

Gnomad NFE exome

AF:

0.000778

Gnomad OTH exome

AF:

0.000328

GnomAD4 exome

AF:

0.000415

AC:

604

AN:

1456536

Hom.:

Cov.:

138

AF XY:

0.000397

AC XY:

288

AN XY:

724652

show subpopulations

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

African (AFR)

AF:

0.0000301

AC:

AN:

33204

American (AMR)

AF:

0.0000673

AC:

AN:

44580

Ashkenazi Jewish (ASJ)

AF:

0.0000385

AC:

AN:

25992

East Asian (EAS)

AF:

0.00

AC:

AN:

39436

South Asian (SAS)

AF:

0.00

AC:

AN:

86096

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

0.000518

AC:

574

AN:

1108178

Other (OTH)

AF:

0.000283

AC:

AN:

60070

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.247

Heterozygous variant carriers

173

259

346

432

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000155

AC:

AN:

148642

Hom.:

Cov.:

AF XY:

0.000179

AC XY:

AN XY:

72634

show subpopulations

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

African (AFR)

AF:

0.0000250

AC:

AN:

39938

American (AMR)

AF:

0.00

AC:

AN:

15032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3416

East Asian (EAS)

AF:

0.00

AC:

AN:

4960

South Asian (SAS)

AF:

0.00

AC:

AN:

4754

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10348

Middle Eastern (MID)

AF:

0.00

AC:

AN:

284

European-Non Finnish (NFE)

AF:

0.000328

AC:

AN:

66972

Other (OTH)

AF:

0.00

AC:

AN:

2052

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.262

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000506

Hom.:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00116

AC:

ExAC

AF:

0.000873

AC:

106

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.74

CADD

Benign

0.053

(source)

DANN

Benign

0.58

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00050

LIST_S2

Benign

0.53

M_CAP

Benign

0.0016

MetaRNN

Benign

0.014

MetaSVM

Benign

-0.91

PhyloP100

-4.3

PROVEAN

Benign

-1.1

REVEL

Benign

0.0070

Sift

Benign

0.32

Sift4G

Benign

0.31

Vest4

0.11

MVP

0.030

MPC

0.58

ClinPred

0.017

GERP RS

-2.2

PromoterAI

-0.040

Neutral

(source)

gMVP

0.082

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over