19-15476374-C-T

Position:

• chr19-15476374-C-T

Variant summary

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

The ENST00000340880.5(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 same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.37 (10568 hom., cov: 32)
  • Exomes 𝑓: 0.38 (105631 hom.)
• Consequence: PGLYRP2 ENST00000340880.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.436

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=0.0014637709).
• 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/exons	MANE	Protein	UniProt
PGLYRP2	NM_052890.4	c.296G>A	p.Arg99Gln	missense_variant	2/5	ENST00000340880.5	NP_443122.3
PGLYRP2	NM_001363546.1	c.296G>A	p.Arg99Gln	missense_variant	2/4		NP_001350475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP2	ENST00000340880.5	c.296G>A	p.Arg99Gln	missense_variant	2/5	1	NM_052890.4	ENSP00000345968	P2
PGLYRP2	ENST00000292609.8	c.296G>A	p.Arg99Gln	missense_variant	2/4	1		ENSP00000292609	A2
PGLYRP2	ENST00000601792.1	c.404G>A	p.Arg135Gln	missense_variant	4/4	4		ENSP00000472856
PGLYRP2	ENST00000594637.1	c.296G>A	p.Arg99Gln	missense_variant	3/3	4		ENSP00000470112

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

GnomAD3 exomes AF: 0.362 AC: 90868 AN: 251298 Hom.: 16732 AF XY: 0.360 AC XY: 48954 AN XY: 135820

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

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.: 32 AF XY: 0.375 AC XY: 27845 AN XY: 74282

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	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;.;.
MutationTaster	Benign	1.0	P;P
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

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: rs733731; hg19: chr19-15587185; COSMIC: COSV52994294;