7-139483567-C-G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_198508.4(KLRG2):c.76G>C(p.Val26Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KLRG2 NM_198508.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.648

Genes affected

KLRG2 (HGNC:24778): (killer cell lectin like receptor G2) Predicted to enable carbohydrate binding activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.057185978).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRG2	NM_198508.4	c.76G>C	p.Val26Leu	missense_variant	1/5	ENST00000340940.5
KLRG2	XM_011516140.3	c.76G>C	p.Val26Leu	missense_variant	1/4
KLRG2	XM_011516141.3	c.76G>C	p.Val26Leu	missense_variant	1/4
KLRG2	XM_005250311.4	c.76G>C	p.Val26Leu	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRG2	ENST00000340940.5	c.76G>C	p.Val26Leu	missense_variant	1/5	1	NM_198508.4	P1
KLRG2	ENST00000393039.2	c.76G>C	p.Val26Leu	missense_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

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

Jun 21, 2022

The c.76G>C (p.V26L) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a G to C substitution at nucleotide position 76, causing the valine (V) at amino acid position 26 to be replaced by a leucine (L). 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	Benign	0.11
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	2.3
Dann	Benign	0.71
DEOGEN2	Benign	0.0029	T;.
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.49	T;T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.057	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.34	N;N
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-0.44	N;N
REVEL	Benign	0.047
Sift	Benign	0.15	T;T
Sift4G	Benign	0.24	T;T
Polyphen		0.0	B;B
Vest4		0.018
MutPred		0.074		Gain of glycosylation at T28 (P = 0.1915);Gain of glycosylation at T28 (P = 0.1915);
MVP		0.16
MPC		0.79
ClinPred		0.050	T
GERP RS		-0.069
Varity_R		0.047
gMVP		0.076

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

Other links and lift over

dbSNP: rs1248499400; hg19: chr7-139168313;