chr7-139454204-C-G

Variant names:

• chr7-139454204-C-G
• rs17160911
• NM_198508.4:c.1016G>C

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 20 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: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198508.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG2	NM_198508.4	MANE Select	c.1016G>C	p.Gly339Ala	missense	Exon 4 of 5	NP_940910.1	A4D1S0-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLRG2	ENST00000340940.5	TSL:1 MANE Select	c.1016G>C	p.Gly339Ala	missense	Exon 4 of 5	ENSP00000339356.4	A4D1S0-1
	KLRG2	ENST00000869133.1		c.1067G>C	p.Gly356Ala	missense	Exon 5 of 6	ENSP00000539192.1
	KLRG2	ENST00000941714.1		c.914G>C	p.Gly305Ala	missense	Exon 3 of 4	ENSP00000611773.1

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

GnomAD2 exomes AF: 0.134 AC: 20202 AN: 150352 AF XY: 0.134

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 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

African (AFR) AF: 0.190 AC: 5853 AN: 30728

American (AMR) AF: 0.111 AC: 3909 AN: 35128

Ashkenazi Jewish (ASJ) AF: 0.106 AC: 2646 AN: 24894

East Asian (EAS) AF: 0.179 AC: 6355 AN: 35530

South Asian (SAS) AF: 0.149 AC: 11727 AN: 78488

European-Finnish (FIN) AF: 0.0948 AC: 4614 AN: 48682

Middle Eastern (MID) AF: 0.155 AC: 852 AN: 5498

European-Non Finnish (NFE) AF: 0.132 AC: 138498 AN: 1049768

Other (OTH) AF: 0.140 AC: 7975 AN: 56852

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

African (AFR) AF: 0.195 AC: 8089 AN: 41468

American (AMR) AF: 0.124 AC: 1888 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.105 AC: 364 AN: 3470

East Asian (EAS) AF: 0.202 AC: 1039 AN: 5148

South Asian (SAS) AF: 0.156 AC: 752 AN: 4814

European-Finnish (FIN) AF: 0.0915 AC: 968 AN: 10584

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.136 AC: 9216 AN: 67964

Other (OTH) AF: 0.160 AC: 337 AN: 2112

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 v4.9

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
PhyloP100		0.31
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
Mutation Taster		=97/3	polymorphism (auto)

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