rs892145

Positions:

• chr19-15475861-A-T

Variant summary

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

The NM_052890.4(PGLYRP2):​c.809T>A​(p.Met270Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.372 in 1,613,702 control chromosomes in the GnomAD database, including 112,897 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 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 0.38 (10949 hom., cov: 31)
  • Exomes 𝑓: 0.37 (101948 hom.)
• Consequence: PGLYRP2 NM_052890.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0024980903).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PGLYRP2	NM_052890.4	c.809T>A	p.Met270Lys	missense_variant	2/5	ENST00000340880.5
PGLYRP2	NM_001363546.1	c.809T>A	p.Met270Lys	missense_variant	2/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PGLYRP2	ENST00000340880.5	c.809T>A	p.Met270Lys	missense_variant	2/5	1	NM_052890.4	P2
PGLYRP2	ENST00000292609.8	c.809T>A	p.Met270Lys	missense_variant	2/4	1		A2

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57332 AN: 151804 Hom.: 10947 Cov.: 31

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.396

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.377

Gnomad OTH AF: 0.385

GnomAD3 exomes AF: 0.358 AC: 89600 AN: 250436 Hom.: 16258 AF XY: 0.356 AC XY: 48207 AN XY: 135552

Gnomad AFR exome AF: 0.398

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.299

Gnomad EAS exome AF: 0.349

Gnomad SAS exome AF: 0.302

Gnomad FIN exome AF: 0.388

Gnomad NFE exome AF: 0.371

Gnomad OTH exome AF: 0.365

GnomAD4 exome AF: 0.372 AC: 543487 AN: 1461780 Hom.: 101948 Cov.: 67 AF XY: 0.370 AC XY: 269263 AN XY: 727190

Gnomad4 AFR exome AF: 0.403

Gnomad4 AMR exome AF: 0.349

Gnomad4 ASJ exome AF: 0.297

Gnomad4 EAS exome AF: 0.353

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.379

Gnomad4 OTH exome AF: 0.367

GnomAD4 genome AF: 0.378 AC: 57378 AN: 151922 Hom.: 10949 Cov.: 31 AF XY: 0.381 AC XY: 28276 AN XY: 74228

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.369

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.351

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.396

Gnomad4 NFE AF: 0.377

Gnomad4 OTH AF: 0.387

Alfa AF: 0.371 Hom.: 7990

Bravo AF: 0.378

TwinsUK AF: 0.379 AC: 1406

ALSPAC AF: 0.380 AC: 1463

ESP6500AA AF: 0.388 AC: 1709

ESP6500EA AF: 0.377 AC: 3238

ExAC AF: 0.358 AC: 43436

Asia WGS AF: 0.363 AC: 1264 AN: 3478

EpiCase AF: 0.370

EpiControl AF: 0.370

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.69	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	2.5
DANN	Benign	0.71
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.0025	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.4	M;M
MutationTaster	Benign	1.0	P;P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.048
Sift	Benign	0.14	T;T
Sift4G	Benign	0.14	T;T
Polyphen		0.14	B;B
Vest4		0.13
MPC		0.27
ClinPred		0.014	T
GERP RS		-1.1
Varity_R		0.20
gMVP		0.70

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: rs892145; hg19: chr19-15586672; COSMIC: COSV52994044; COSMIC: COSV52994044;