Variant 12-10435819-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002260.4(KLRC2):c.168T>C(p.Asp56Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00038 in 1,543,740 control chromosomes in the GnomAD database, including 95 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 49 hom., cov: 28)

Exomes 𝑓: 0.00024 ( 46 hom. )

Consequence

KLRC2
NM_002260.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.170

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 -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 12-10435819-A-G is Benign according to our data. Variant chr12-10435819-A-G is described in ClinVar as [Benign]. Clinvar id is 724292.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.17 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 49 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRC2	NM_002260.4 linkuse as main transcript	c.168T>C	p.Asp56Asp	synonymous_variant	1/6	ENST00000381902.7	NP_002251.2	P26717

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRC2	ENST00000381902.7 linkuse as main transcript	c.168T>C	p.Asp56Asp	synonymous_variant	1/6	1	NM_002260.4	ENSP00000371327.2		P26717
ENSG00000255641	ENST00000539033.1 linkuse as main transcript	c.168T>C	p.Asp56Asp	synonymous_variant	1/7	1		ENSP00000437563.1		F5H6K3

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

251

AN:

141752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00650

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000138

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000211

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000929

Gnomad OTH

AF:

0.000519

GnomAD3 exomes

AF:

0.000859

AC:

207

AN:

240958

Hom.:

AF XY:

0.000613

AC XY:

AN XY:

130468

show subpopulations

Gnomad AFR exome

AF:

0.00991

Gnomad AMR exome

AF:

0.000235

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000117

Gnomad SAS exome

AF:

0.0000667

Gnomad FIN exome

AF:

0.0000482

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000512

GnomAD4 exome

AF:

0.000237

AC:

332

AN:

1401868

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

159

AN XY:

698060

show subpopulations

Gnomad4 AFR exome

AF:

0.00545

Gnomad4 AMR exome

AF:

0.000296

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000374

Gnomad4 SAS exome

AF:

0.0000593

Gnomad4 FIN exome

AF:

0.0000390

Gnomad4 NFE exome

AF:

0.0000713

Gnomad4 OTH exome

AF:

0.000850

GnomAD4 genome

AF:

0.00180

AC:

255

AN:

141872

Hom.:

Cov.:

AF XY:

0.00172

AC XY:

119

AN XY:

69152

show subpopulations

Gnomad4 AFR

AF:

0.00658

Gnomad4 AMR

AF:

0.000138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000211

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000929

Gnomad4 OTH

AF:

0.000513

Alfa

AF:

0.00125

Hom.:

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	May 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.6

DANN

Benign

0.46

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