7-139483129-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198508.4(KLRG2):c.514C>A(p.Leu172Met) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: KLRG2 NM_198508.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.337

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13071382).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLRG2	NM_198508.4	c.514C>A	p.Leu172Met	missense_variant	1/5	ENST00000340940.5
KLRG2	XM_011516140.3	c.514C>A	p.Leu172Met	missense_variant	1/4
KLRG2	XM_011516141.3	c.514C>A	p.Leu172Met	missense_variant	1/4
KLRG2	XM_005250311.4	c.514C>A	p.Leu172Met	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLRG2	ENST00000340940.5	c.514C>A	p.Leu172Met	missense_variant	1/5	1	NM_198508.4	P1
KLRG2	ENST00000393039.2	c.514C>A	p.Leu172Met	missense_variant	1/2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1331416 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 656160

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jan 03, 2024

The c.514C>A (p.L172M) alteration is located in exon 1 (coding exon 1) of the KLRG2 gene. This alteration results from a C to A substitution at nucleotide position 514, causing the leucine (L) at amino acid position 172 to be replaced by a methionine (M). 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	0.18
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
Cadd	Benign	18
Dann	Uncertain	0.98
DEOGEN2	Benign	0.0050	T;.
Eigen	Benign	-0.62
Eigen_PC	Benign	-0.84
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.43	T;T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	0.97	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Uncertain	0.57	T
PROVEAN	Benign	-0.19	N;N
REVEL	Benign	0.067
Sift	Uncertain	0.0020	D;D
Sift4G	Benign	0.13	T;T
Polyphen		0.95	P;D
Vest4		0.14
MutPred		0.21		Gain of MoRF binding (P = 0.0659);Gain of MoRF binding (P = 0.0659);
MVP		0.14
MPC		1.8
ClinPred		0.31	T
GERP RS		0.16
Varity_R		0.11
gMVP		0.068

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-139167875;