12-9881621-C-T

Position:

chr12-9881621-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001190765.1(KLRF2):c.26C>T(p.Thr9Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000293 in 1,535,016 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 1 hom. )

Consequence

KLRF2
NM_001190765.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.41

Variant links:

Genes affected

KLRF2 (HGNC:37646): (killer cell lectin like receptor F2) Enables protein homodimerization activity. Predicted to be involved in natural killer cell degranulation and positive regulation of cytokine production. Predicted to act upstream of or within natural killer cell activation and positive regulation of natural killer cell mediated cytotoxicity. Is integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

KLRF2 links:

CLEC2A (HGNC:24191): (C-type lectin domain family 2 member A) Enables protein homodimerization activity. Predicted to be involved in natural killer cell mediated cytotoxicity. Predicted to act upstream of or within several processes, including T cell receptor signaling pathway; regulation of actin filament polymerization; and regulation of interleukin-2 production. Located in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

CLEC2A links:

CLEC2A (HGNC:):

CLEC2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.024168223).

BP6

Variant 12-9881621-C-T is Benign according to our data. Variant chr12-9881621-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2457173.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRF2	NM_001190765.1 linkuse as main transcript	c.26C>T	p.Thr9Met	missense_variant	1/6	ENST00000535540.1	NP_001177694.1	D3W0D1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRF2	ENST00000535540.1 linkuse as main transcript	c.26C>T	p.Thr9Met	missense_variant	1/6	1	NM_001190765.1	ENSP00000438244.1		D3W0D1

Frequencies

GnomAD3 genomes

AF:

0.000224

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000426

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000193

AC:

AN:

134450

Hom.:

AF XY:

0.000205

AC XY:

AN XY:

73226

show subpopulations

Gnomad AFR exome

AF:

0.000155

Gnomad AMR exome

AF:

0.0000409

Gnomad ASJ exome

AF:

0.000121

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000445

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.000379

Gnomad OTH exome

AF:

0.000242

GnomAD4 exome

AF:

0.000301

AC:

416

AN:

1382902

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

200

AN XY:

682472

show subpopulations

Gnomad4 AFR exome

AF:

0.000158

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.0000795

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.0000885

Gnomad4 NFE exome

AF:

0.000361

Gnomad4 OTH exome

AF:

0.000225

GnomAD4 genome

AF:

0.000224

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000426

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000342

Hom.:

Bravo

AF:

0.000219

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000129

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 01, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.16

DANN

Benign

0.42

DEOGEN2

Benign

0.020

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.27

M_CAP

Benign

0.00085

MetaRNN

Benign

0.024

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.34

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.6

REVEL

Benign

0.012

Sift

Benign

0.21

Sift4G

Benign

0.34

Vest4

0.097

MutPred

0.38

Gain of sheet (P = 0.0344);

MVP

0.061

ClinPred

0.012

GERP RS

-4.5

Varity_R

0.014

gMVP

0.093

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