Variant 12-10435982-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_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. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in the same amino acid substitution has been previously reported as Likely benign in UniProt.

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

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.0290

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=0.0028169751).

BP6

Variant 12-10435982-T-C is Benign according to our data. Variant chr12-10435982-T-C is described in ClinVar as [Benign]. Clinvar id is 769387.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC2	NM_002260.4 link	c.5A>G	p.Asn2Ser	missense_variant	1/6	ENST00000381902.7	NP_002251.2	P26717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
KLRC2	ENST00000381902.7 link	c.5A>G	p.Asn2Ser	missense_variant	1/6	1	NM_002260.4	ENSP00000371327.2	P26717
ENSG00000255641	ENST00000539033.1 link	c.5A>G	p.Asn2Ser	missense_variant	1/7	1		ENSP00000437563.1	F5H6K3
KLRC2	ENST00000381901.5 link	c.5A>G	p.Asn2Ser	missense_variant	1/6	5		ENSP00000371326.1	J3KPJ4
KLRC2	ENST00000536833.6 link	c.11-572A>G		intron_variant		5		ENSP00000444754.1	F5H518

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

57073

AN:

145900

Hom.:

455

Cov.:

FAILED QC

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

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

show subpopulations

Gnomad4 AFR exome

AF:

0.188

Gnomad4 AMR exome

AF:

0.428

Gnomad4 ASJ exome

AF:

0.415

Gnomad4 EAS exome

AF:

0.410

Gnomad4 SAS exome

AF:

0.391

Gnomad4 FIN exome

AF:

0.438

Gnomad4 NFE exome

AF:

0.441

Gnomad4 OTH exome

AF:

0.416

GnomAD4 genome

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

AF:

0.391

AC:

57094

AN:

146024

Hom.:

453

Cov.:

AF XY:

0.391

AC XY:

27881

AN XY:

71218

show subpopulations

Gnomad4 AFR

AF:

0.242

Gnomad4 AMR

AF:

0.441

Gnomad4 ASJ

AF:

0.418

Gnomad4 EAS

AF:

0.424

Gnomad4 SAS

AF:

0.401

Gnomad4 FIN

AF:

0.453

Gnomad4 NFE

AF:

0.454

Gnomad4 OTH

AF:

0.414

Alfa

AF:

0.362

Hom.:

ExAC

AF:

0.393

AC:

47741

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.41

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

LIST_S2

Benign

0.67

T;.;T

MetaRNN

Benign

0.0028

T;T;T

MetaSVM

Benign

-0.87

PROVEAN

Uncertain

-2.6

D;N;N

REVEL

Benign

0.013

Sift

Benign

0.34

T;T;T

Sift4G

Benign

0.15

T;T;T

Vest4

0.058

MPC

0.37

ClinPred

0.0067

GERP RS

-0.46

gMVP

0.049

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