chr12-9884978-G-C

Position:

• chr12-9884978-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001190765.1(KLRF2):​c.115G>C​(p.Gly39Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KLRF2 NM_001190765.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.00800

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]

CLEC2A (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRF2	NM_001190765.1	c.115G>C	p.Gly39Arg	missense_variant	2/6	ENST00000535540.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRF2	ENST00000535540.1	c.115G>C	p.Gly39Arg	missense_variant	2/6	1	NM_001190765.1	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 21

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 29, 2023

The c.115G>C (p.G39R) alteration is located in exon 2 (coding exon 2) of the KLRF2 gene. This alteration results from a G to C substitution at nucleotide position 115, causing the glycine (G) at amino acid position 39 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.66
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.92
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.50	T
M_CAP	Benign	0.0019	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.55	N
MutationTaster	Benign	1.0	N
PrimateAI	Uncertain	0.54	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.17
Sift	Uncertain	0.014	D
Sift4G	Benign	0.067	T
Vest4		0.54
MutPred		0.61		Gain of catalytic residue at L34 (P = 5e-04);
MVP		0.29
ClinPred		0.48	T
GERP RS		0.88
Varity_R		0.18
gMVP		0.21

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr12-10037577;