Genetic Variant PGLYRP2:p.Arg99Gln (chr19-15476374-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_052890.4(PGLYRP2):c.296G>A(p.Arg99Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,613,796 control chromosomes in the GnomAD database, including 116,199 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 the same amino acid substitution has been previously reported as Likely benign in UniProt.

Frequency

Genomes: 𝑓 0.37 ( 10568 hom., cov: 32)

Exomes 𝑓: 0.38 ( 105631 hom. )

Consequence

PGLYRP2
NM_052890.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.436

Variant links:

Genes affected

PGLYRP2 (HGNC:30013): (peptidoglycan recognition protein 2) This gene encodes a peptidoglycan recognition protein, which belongs to the N-acetylmuramoyl-L-alanine amidase 2 family. This protein hydrolyzes the link between N-acetylmuramoyl residues and L-amino acid residues in bacterial cell wall glycopeptides, and thus may play a scavenger role by digesting biologically active peptidoglycan into biologically inactive fragments. [provided by RefSeq, Sep 2011]

PGLYRP2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014637709).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGLYRP2	NM_052890.4 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 5	ENST00000340880.5	NP_443122.3	Q96PD5-1
PGLYRP2	NM_001363546.1 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 4		NP_001350475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGLYRP2	ENST00000340880.5 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 5	1	NM_052890.4	ENSP00000345968.4	Q96PD5-1
PGLYRP2	ENST00000292609.8 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 4	1		ENSP00000292609.3	Q96PD5-2
PGLYRP2	ENST00000601792.1 link	c.404G>A	p.Arg135Gln	missense_variant	Exon 4 of 4	4		ENSP00000472856.2	M0R2W8
PGLYRP2	ENST00000594637.1 link	c.296G>A	p.Arg99Gln	missense_variant	Exon 3 of 3	4		ENSP00000470112.1	M0QYW3

Frequencies

GnomAD3 genomes

AF:

0.371

AC:

56313

AN:

151856

Hom.:

10570

Cov.:

show subpopulations

Gnomad AFR

AF:

0.348

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.367

Gnomad ASJ

AF:

0.300

Gnomad EAS

AF:

0.351

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.428

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.385

Gnomad OTH

AF:

0.384

GnomAD3 exomes

AF:

0.362

AC:

90868

AN:

251298

Hom.:

16732

AF XY:

0.360

AC XY:

48954

AN XY:

135820

show subpopulations

Gnomad AFR exome

AF:

0.347

Gnomad AMR exome

AF:

0.345

Gnomad ASJ exome

AF:

0.309

Gnomad EAS exome

AF:

0.350

Gnomad SAS exome

AF:

0.302

Gnomad FIN exome

AF:

0.417

Gnomad NFE exome

AF:

0.380

Gnomad OTH exome

AF:

0.370

GnomAD4 exome

AF:

0.378

AC:

552813

AN:

1461822

Hom.:

105631

Cov.:

AF XY:

0.377

AC XY:

273849

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.350

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.307

Gnomad4 EAS exome

AF:

0.354

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.417

Gnomad4 NFE exome

AF:

0.388

Gnomad4 OTH exome

AF:

0.370

GnomAD4 genome

AF:

0.371

AC:

56349

AN:

151974

Hom.:

10568

Cov.:

AF XY:

0.375

AC XY:

27845

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.348

Gnomad4 AMR

AF:

0.368

Gnomad4 ASJ

AF:

0.300

Gnomad4 EAS

AF:

0.350

Gnomad4 SAS

AF:

0.300

Gnomad4 FIN

AF:

0.428

Gnomad4 NFE

AF:

0.385

Gnomad4 OTH

AF:

0.387

Alfa

AF:

0.370

Hom.:

25773

Bravo

AF:

0.366

TwinsUK

AF:

0.388

AC:

1438

ALSPAC

AF:

0.387

AC:

1491

ESP6500AA

AF:

0.344

AC:

1516

ESP6500EA

AF:

0.386

AC:

3316

ExAC

AF:

0.361

AC:

43837

Asia WGS

AF:

0.355

AC:

1234

AN:

3478

EpiCase

AF:

0.377

EpiControl

AF:

0.377

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.83

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.14

DANN

Benign

0.50

DEOGEN2

Benign

0.038

.;T;T;T

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.0023

LIST_S2

Benign

0.68

T;T;T;T

MetaRNN

Benign

0.0015

T;T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

0.17

N;N;.;.

PrimateAI

Benign

0.22

PROVEAN

Benign

0.42

N;N;.;.

REVEL

Benign

0.066

Sift

Benign

0.89

T;T;.;.

Sift4G

Benign

0.56

T;T;T;.

Polyphen

0.030

B;B;.;.

Vest4

0.013

MPC

0.19

ClinPred

0.0041

GERP RS

-5.8

Varity_R

0.027

gMVP

0.13

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over