7-139483038-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198508.4(KLRG2):​c.605G>C​(p.Arg202Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000817 in 1,223,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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: not found (cov: 32)
  • Exomes 𝑓: 8.2e-7 (0 hom.)
• Consequence: KLRG2 NM_198508.4 missense
• Clinical Significance: Not reported in ClinVar
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077225655).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLRG2	NM_198508.4	c.605G>C	p.Arg202Pro	missense_variant	Exon 1 of 5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516140.3	c.605G>C	p.Arg202Pro	missense_variant	Exon 1 of 4		XP_011514442.1
KLRG2	XM_011516141.3	c.605G>C	p.Arg202Pro	missense_variant	Exon 1 of 4		XP_011514443.1
KLRG2	XM_005250311.4	c.605G>C	p.Arg202Pro	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>C	p.Arg202Pro	missense_variant	Exon 1 of 5	1	NM_198508.4	ENSP00000339356.4
KLRG2	ENST00000393039.2	c.605G>C	p.Arg202Pro	missense_variant	Exon 1 of 2	5		ENSP00000376759.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.18e-7 AC: 1 AN: 1223242 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 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: 0.0000365 AC: 1 AN: 27370

South Asian (SAS) AF: 0.00 AC: 0 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: 0.00 AC: 0 AN: 1007338

Other (OTH) AF: 0.00 AC: 0 AN: 50468

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	9.4
DANN	Benign	0.97
DEOGEN2	Benign	0.0040	T;.
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;L
PhyloP100		-0.083
PrimateAI	Uncertain	0.59	T
PROVEAN	Benign	-0.49	N;N
REVEL	Benign	0.047
Sift	Benign	0.12	T;T
Sift4G	Benign	0.35	T;T
Polyphen		0.0040	B;B
Vest4		0.055
MutPred		0.17		Gain of glycosylation at R202 (P = 0.0571);Gain of glycosylation at R202 (P = 0.0571);
MVP		0.17
MPC		1.7
ClinPred		0.16	T
GERP RS		1.1
Varity_R		0.10
gMVP		0.12
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;