7-139483038-C-A

Variant names:

• chr7-139483038-C-A
• rs530838230
• NM_198508.4:c.605G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_198508.4(KLRG2):​c.605G>T​(p.Arg202Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000349 in 1,375,474 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R202W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (1 hom.)
• Consequence: KLRG2 NM_198508.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0830
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04937896).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRG2	NM_198508.4	c.605G>T	p.Arg202Leu	missense_variant	Exon 1 of 5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516140.3	c.605G>T	p.Arg202Leu	missense_variant	Exon 1 of 4		XP_011514442.1
KLRG2	XM_011516141.3	c.605G>T	p.Arg202Leu	missense_variant	Exon 1 of 4		XP_011514443.1
KLRG2	XM_005250311.4	c.605G>T	p.Arg202Leu	missense_variant	Exon 1 of 4		XP_005250368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLRG2	ENST00000340940.5	c.605G>T	p.Arg202Leu	missense_variant	Exon 1 of 5	1	NM_198508.4	ENSP00000339356.4
KLRG2	ENST00000393039.2	c.605G>T	p.Arg202Leu	missense_variant	Exon 1 of 2	5		ENSP00000376759.2

Frequencies

GnomAD3 genomes AF: 0.0000197 AC: 3 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00 AC: 0 AN: 3456 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000368 AC: 45 AN: 1223242 Hom.: 1 Cov.: 31 AF XY: 0.0000573 AC XY: 34 AN XY: 593772

African (AFR) AF: 0.00 AC: 0 AN: 23874

American (AMR) AF: 0.00 AC: 0 AN: 10040

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17136

East Asian (EAS) AF: 0.00 AC: 0 AN: 27370

South Asian (SAS) AF: 0.000764 AC: 41 AN: 53694

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 29818

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3504

European-Non Finnish (NFE) AF: 9.93e-7 AC: 1 AN: 1007338

Other (OTH) AF: 0.0000594 AC: 3 AN: 50468

GnomAD4 genome AF: 0.0000197 AC: 3 AN: 152232 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74428

African (AFR) AF: 0.00 AC: 0 AN: 41556

American (AMR) AF: 0.00 AC: 0 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5152

South Asian (SAS) AF: 0.000621 AC: 3 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67992

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.0000936 AC: 5

Asia WGS AF: 0.000868 AC: 3 AN: 3472

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.605G>T (p.R202L) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a G to T substitution at nucleotide position 605, causing the arginine (R) at amino acid position 202 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	0.13
BayesDel_addAF	Benign	-0.23	T
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.3
DANN	Benign	0.94
DEOGEN2	Benign	0.0033	T;.
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.061	N
LIST_S2	Benign	0.58	T;T
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.049	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
PhyloP100		-0.083
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.86	N;N
REVEL	Benign	0.022
Sift	Benign	0.17	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.36	B;B
Vest4		0.089
MutPred		0.21		Gain of catalytic residue at R202 (P = 0.0579);Gain of catalytic residue at R202 (P = 0.0579);
MVP		0.11
MPC		1.1
ClinPred		0.12	T
GERP RS		1.1
Varity_R		0.046
gMVP		0.13
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs530838230; hg19: chr7-139167784;