rs17160911

Positions:

• chr7-139454204-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198508.4(KLRG2):​c.1016G>C​(p.Gly339Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 1,517,600 control chromosomes in the GnomAD database, including 14,535 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 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 nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.15 (1917 hom., cov: 31)
  • Exomes 𝑓: 0.13 (12618 hom.)
• Consequence: KLRG2 NM_198508.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.312

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015237927).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLRG2	NM_198508.4	c.1016G>C	p.Gly339Ala	missense_variant	4/5	ENST00000340940.5	NP_940910.1
KLRG2	XM_011516141.3	c.1005+25423G>C		intron_variant			XP_011514443.1
KLRG2	XM_005250311.4	c.1006-497G>C		intron_variant			XP_005250368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLRG2	ENST00000340940.5	c.1016G>C	p.Gly339Ala	missense_variant	4/5	1	NM_198508.4	ENSP00000339356.4
KLRG2	ENST00000393039.2	c.758-497G>C		intron_variant		5		ENSP00000376759.2

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22776 AN: 151914 Hom.: 1914 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.124

Gnomad ASJ AF: 0.105

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0915

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.136

Gnomad OTH AF: 0.155

GnomAD3 exomes AF: 0.134 AC: 20202 AN: 150352 Hom.: 1486 AF XY: 0.134 AC XY: 10764 AN XY: 80038

Gnomad AFR exome AF: 0.195

Gnomad AMR exome AF: 0.107

Gnomad ASJ exome AF: 0.107

Gnomad EAS exome AF: 0.208

Gnomad SAS exome AF: 0.148

Gnomad FIN exome AF: 0.0951

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.132

GnomAD4 exome AF: 0.134 AC: 182429 AN: 1365568 Hom.: 12618 Cov.: 26 AF XY: 0.134 AC XY: 90442 AN XY: 675408

Gnomad4 AFR exome AF: 0.190

Gnomad4 AMR exome AF: 0.111

Gnomad4 ASJ exome AF: 0.106

Gnomad4 EAS exome AF: 0.179

Gnomad4 SAS exome AF: 0.149

Gnomad4 FIN exome AF: 0.0948

Gnomad4 NFE exome AF: 0.132

Gnomad4 OTH exome AF: 0.140

GnomAD4 genome AF: 0.150 AC: 22800 AN: 152032 Hom.: 1917 Cov.: 31 AF XY: 0.147 AC XY: 10942 AN XY: 74300

Gnomad4 AFR AF: 0.195

Gnomad4 AMR AF: 0.124

Gnomad4 ASJ AF: 0.105

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.156

Gnomad4 FIN AF: 0.0915

Gnomad4 NFE AF: 0.136

Gnomad4 OTH AF: 0.160

Alfa AF: 0.135 Hom.: 1059

Bravo AF: 0.154

TwinsUK AF: 0.126 AC: 468

ALSPAC AF: 0.138 AC: 531

ExAC AF: 0.0771 AC: 3363

Asia WGS AF: 0.177 AC: 616 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	12
DANN	Benign	0.83
DEOGEN2	Benign	0.00057	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.62
FATHMM_MKL	Benign	0.17	N
LIST_S2	Benign	0.54	T
MetaRNN	Benign	0.0015	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.30	T
PROVEAN	Benign	0.89	N
REVEL	Benign	0.028
Sift	Benign	0.61	T
Sift4G	Benign	0.48	T
Polyphen		0.026	B
Vest4		0.058
MPC		0.016
ClinPred		0.0012	T
GERP RS		2.9
Varity_R		0.038
gMVP		0.28

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: rs17160911; hg19: chr7-139138950; COSMIC: COSV61800388;