Genetic Variant KLRC2:p.Arg19Pro (chr12-10435931-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_002260.4(KLRC2):c.56G>C(p.Arg19Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 2 hom., cov: 30)

Exomes 𝑓: 0.37 ( 8 hom. )

Failed GnomAD Quality Control

Consequence

KLRC2
NM_002260.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.132

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0020274222).

BP6

Variant 12-10435931-C-G is Benign according to our data. Variant chr12-10435931-C-G is described in ClinVar as [Benign]. Clinvar id is 769386.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRC2	NM_002260.4 link	c.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 6	ENST00000381902.7	NP_002251.2	P26717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRC2	ENST00000381902.7 link	c.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 6	1	NM_002260.4	ENSP00000371327.2		P26717
ENSG00000255641	ENST00000539033.1 link	c.56G>C	p.Arg19Pro	missense_variant	Exon 1 of 7	1		ENSP00000437563.1		F5H6K3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

20211

AN:

89826

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0772

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.249

Gnomad ASJ

AF:

0.265

Gnomad EAS

AF:

0.210

Gnomad SAS

AF:

0.177

Gnomad FIN

AF:

0.274

Gnomad MID

AF:

0.136

Gnomad NFE

AF:

0.327

Gnomad OTH

AF:

0.243

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR;InbreedingCoeff

AF:

0.367

AC:

399928

AN:

1089756

Hom.:

Cov.:

144

AF XY:

0.361

AC XY:

194153

AN XY:

537798

show subpopulations

Gnomad4 AFR exome

AF:

0.111

Gnomad4 AMR exome

AF:

0.257

Gnomad4 ASJ exome

AF:

0.252

Gnomad4 EAS exome

AF:

0.209

Gnomad4 SAS exome

AF:

0.192

Gnomad4 FIN exome

AF:

0.298

Gnomad4 NFE exome

AF:

0.402

Gnomad4 OTH exome

AF:

0.316

GnomAD4 genome

Data not reliable, filtered out with message: InbreedingCoeff

AF:

0.225

AC:

20215

AN:

89934

Hom.:

Cov.:

AF XY:

0.224

AC XY:

9903

AN XY:

44180

show subpopulations

Gnomad4 AFR

AF:

0.0770

Gnomad4 AMR

AF:

0.249

Gnomad4 ASJ

AF:

0.265

Gnomad4 EAS

AF:

0.210

Gnomad4 SAS

AF:

0.177

Gnomad4 FIN

AF:

0.274

Gnomad4 NFE

AF:

0.327

Gnomad4 OTH

AF:

0.243

Alfa

AF:

0.209

Hom.:

ExAC

AF:

0.411

AC:

49916

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

0.98

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.75

FATHMM_MKL

Benign

0.0018

LIST_S2

Uncertain

0.89

D;.;D

MetaRNN

Benign

0.0020

T;T;T

MetaSVM

Benign

-0.90

PROVEAN

Pathogenic

-5.3

D;D;D

REVEL

Benign

0.019

Sift

Uncertain

0.021

D;D;D

Sift4G

Uncertain

0.0070

D;D;D

Vest4

0.085

MPC

1.6

ClinPred

0.078

GERP RS

-0.058

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over