7-139483198-G-C

Position:

• chr7-139483198-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_198508.4(KLRG2):​c.445C>G​(p.Arg149Gly) 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. 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: 2.42

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.351369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG2	NM_198508.4	c.445C>G	p.Arg149Gly	missense_variant	1/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516140.3	c.445C>G	p.Arg149Gly	missense_variant	1/4		XP_011514442.1
KLRG2	XM_011516141.3	c.445C>G	p.Arg149Gly	missense_variant	1/4		XP_011514443.1
KLRG2	XM_005250311.4	c.445C>G	p.Arg149Gly	missense_variant	1/4		XP_005250368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG2	ENST00000340940.5	c.445C>G	p.Arg149Gly	missense_variant	1/5	1	NM_198508.4	ENSP00000339356	P1
KLRG2	ENST00000393039.2	c.445C>G	p.Arg149Gly	missense_variant	1/2	5		ENSP00000376759

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 37

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

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

Oct 14, 2021

The c.445C>G (p.R149G) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a C to G substitution at nucleotide position 445, causing the arginine (R) at amino acid position 149 to be replaced by a glycine (G). 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	0.33
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0059	T;.
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Benign	0.68	D
LIST_S2	Benign	0.62	T;T
M_CAP	Pathogenic	0.48	D
MetaRNN	Benign	0.35	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	0.79	N;N
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.6	N;D
REVEL	Benign	0.12
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.33	T;T
Polyphen		1.0	D;D
Vest4		0.19
MutPred		0.25		Loss of methylation at R149 (P = 0.07);Loss of methylation at R149 (P = 0.07);
MVP		0.40
MPC		2.1
ClinPred		0.88	D
GERP RS		3.4
Varity_R		0.55
gMVP		0.29

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: rs1267931807; hg19: chr7-139167944;