19-15476534-T-C

Variant names:

• chr19-15476534-T-C
• rs3813135
• NM_052890.4:c.136A>G

Variant summary

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

The NM_052890.4(PGLYRP2):​c.136A>G​(p.Thr46Ala) 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 1,613,350 control chromosomes in the GnomAD database, including 115,879 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 (10545 hom., cov: 32)
  • Exomes 𝑓: 0.38 (105334 hom.)
• Consequence: PGLYRP2 NM_052890.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0330
• Publications: 31 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=9.975433E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.381 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGLYRP2	NM_052890.4	c.136A>G	p.Thr46Ala	missense_variant	Exon 2 of 5	ENST00000340880.5	NP_443122.3
PGLYRP2	NM_001363546.1	c.136A>G	p.Thr46Ala	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.136A>G	p.Thr46Ala	missense_variant	Exon 2 of 5	1	NM_052890.4	ENSP00000345968.4
PGLYRP2	ENST00000292609.8	c.136A>G	p.Thr46Ala	missense_variant	Exon 2 of 4	1		ENSP00000292609.3
PGLYRP2	ENST00000601792.1	c.244A>G	p.Thr82Ala	missense_variant	Exon 4 of 4	4		ENSP00000472856.2
PGLYRP2	ENST00000594637.1	c.136A>G	p.Thr46Ala	missense_variant	Exon 3 of 3	4		ENSP00000470112.1

Frequencies

GnomAD3 genomes AF: 0.371 AC: 56264 AN: 151848 Hom.: 10546 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.367

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.354

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.385

Gnomad OTH AF: 0.384

GnomAD2 exomes AF: 0.361 AC: 90370 AN: 250064 AF XY: 0.360

Gnomad AFR exome AF: 0.346

Gnomad AMR exome AF: 0.345

Gnomad ASJ exome AF: 0.309

Gnomad EAS exome AF: 0.353

Gnomad FIN exome AF: 0.417

Gnomad NFE exome AF: 0.380

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.378 AC: 552035 AN: 1461384 Hom.: 105334 Cov.: 58 AF XY: 0.376 AC XY: 273467 AN XY: 726940

African (AFR) AF: 0.350 AC: 11714 AN: 33476

American (AMR) AF: 0.348 AC: 15550 AN: 44630

Ashkenazi Jewish (ASJ) AF: 0.307 AC: 8032 AN: 26126

East Asian (EAS) AF: 0.356 AC: 14148 AN: 39690

South Asian (SAS) AF: 0.301 AC: 25946 AN: 86194

European-Finnish (FIN) AF: 0.417 AC: 22238 AN: 53356

Middle Eastern (MID) AF: 0.331 AC: 1907 AN: 5760

European-Non Finnish (NFE) AF: 0.387 AC: 430175 AN: 1111776

Other (OTH) AF: 0.370 AC: 22325 AN: 60376

GnomAD4 genome AF: 0.370 AC: 56300 AN: 151966 Hom.: 10545 Cov.: 32 AF XY: 0.375 AC XY: 27851 AN XY: 74260

African (AFR) AF: 0.348 AC: 14414 AN: 41448

American (AMR) AF: 0.367 AC: 5610 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1043 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1823 AN: 5162

South Asian (SAS) AF: 0.301 AC: 1447 AN: 4814

European-Finnish (FIN) AF: 0.429 AC: 4534 AN: 10564

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

European-Non Finnish (NFE) AF: 0.385 AC: 26133 AN: 67932

Other (OTH) AF: 0.387 AC: 816 AN: 2106

Alfa AF: 0.372 Hom.: 26956

Bravo AF: 0.366

TwinsUK AF: 0.388 AC: 1438

ALSPAC AF: 0.386 AC: 1488

ESP6500AA AF: 0.343 AC: 1512

ESP6500EA AF: 0.385 AC: 3310

ExAC AF: 0.361 AC: 43792

Asia WGS AF: 0.358 AC: 1245 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	0.061
BayesDel_addAF	Benign	-0.85	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.36
DANN	Benign	0.14
DEOGEN2	Benign	0.035	.;T;T;T
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.00025	N
LIST_S2	Benign	0.26	T;T;T;T
MetaRNN	Benign	0.0010	T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-1.8	N;N;.;.
PhyloP100		-0.033
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.81	N;N;.;.
REVEL	Benign	0.072
Sift	Benign	1.0	T;T;.;.
Sift4G	Benign	1.0	T;T;T;.
Polyphen		0.0	B;B;.;.
Vest4		0.013
MPC		0.16
ClinPred		0.0032	T
GERP RS		2.0
Varity_R		0.021
gMVP		0.18
Mutation Taster		=99/1	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: rs3813135; hg19: chr19-15587345; COSMIC: COSV52992301;