NM_052890.4:c.296G>A

Variant names:

• chr19-15476374-C-T
• rs733731
• NM_052890.4:c.296G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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. 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 0.37 (10568 hom., cov: 32)
  • Exomes 𝑓: 0.38 (105631 hom.)
• Consequence: PGLYRP2 NM_052890.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436
• Publications: 36 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 5	ENST00000340880.5	NP_443122.3
PGLYRP2	NM_001363546.1	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	Appris	UniProt
PGLYRP2	ENST00000340880.5	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 5	1	NM_052890.4	ENSP00000345968.4
PGLYRP2	ENST00000292609.8	c.296G>A	p.Arg99Gln	missense_variant	Exon 2 of 4	1		ENSP00000292609.3
PGLYRP2	ENST00000601792.1	c.404G>A	p.Arg135Gln	missense_variant	Exon 4 of 4	4		ENSP00000472856.2
PGLYRP2	ENST00000594637.1	c.296G>A	p.Arg99Gln	missense_variant	Exon 3 of 3	4		ENSP00000470112.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56313 AN: 151856 Hom.: 10570 Cov.: 32

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

GnomAD2 exomes AF: 0.362 AC: 90868 AN: 251298 AF XY: 0.360

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 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.: 67 AF XY: 0.377 AC XY: 273849 AN XY: 727208

African (AFR) AF: 0.350 AC: 11722 AN: 33480

American (AMR) AF: 0.348 AC: 15573 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8033 AN: 26126

East Asian (EAS) AF: 0.354 AC: 14046 AN: 39700

South Asian (SAS) AF: 0.301 AC: 25920 AN: 86252

European-Finnish (FIN) AF: 0.417 AC: 22258 AN: 53418

Middle Eastern (MID) AF: 0.330 AC: 1904 AN: 5768

European-Non Finnish (NFE) AF: 0.388 AC: 431020 AN: 1111968

Other (OTH) AF: 0.370 AC: 22337 AN: 60390

GnomAD4 genome AF: 0.371 AC: 56349 AN: 151974 Hom.: 10568 Cov.: 32 AF XY: 0.375 AC XY: 27845 AN XY: 74282

African (AFR) AF: 0.348 AC: 14433 AN: 41468

American (AMR) AF: 0.368 AC: 5607 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.300 AC: 1041 AN: 3468

East Asian (EAS) AF: 0.350 AC: 1805 AN: 5150

South Asian (SAS) AF: 0.300 AC: 1445 AN: 4814

European-Finnish (FIN) AF: 0.428 AC: 4520 AN: 10560

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.385 AC: 26190 AN: 67946

Other (OTH) AF: 0.387 AC: 819 AN: 2116

Alfa AF: 0.370 Hom.: 35263

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	T
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	N
LIST_S2	Benign	0.68	T;T;T;T
MetaRNN	Benign	0.0015	T;T;T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.17	N;N;.;.
PhyloP100		-0.44
PrimateAI	Benign	0.22	T
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	T
GERP RS		-5.8
Varity_R		0.027
gMVP		0.13
Mutation Taster		=98/2	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: rs733731; hg19: chr19-15587185; COSMIC: COSV52994294;