Genetic Variant NM_052890.4:c.809T>A (chr19-15475861-A-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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. 14/21 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 0.38 ( 10949 hom., cov: 31)

Exomes 𝑓: 0.37 ( 101948 hom. )

Consequence

PGLYRP2
NM_052890.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0960

Publications

40 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
PGLYRP2	NM_052890.4 link	c.809T>A	p.Met270Lys	missense_variant	Exon 2 of 5	ENST00000340880.5	NP_443122.3
PGLYRP2	NM_001363546.1 link	c.809T>A	p.Met270Lys	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 link	c.809T>A	p.Met270Lys	missense_variant	Exon 2 of 5	1	NM_052890.4	ENSP00000345968.4
PGLYRP2	ENST00000292609.8 link	c.809T>A	p.Met270Lys	missense_variant	Exon 2 of 4	1		ENSP00000292609.3

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

57332

AN:

151804

Hom.:

10947

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.358

AC:

89600

AN:

250436

AF XY:

0.356

show subpopulations

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 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.:

AF XY:

0.370

AC XY:

269263

AN XY:

727190

show subpopulations

African (AFR)

AF:

0.403

AC:

13485

AN:

33480

American (AMR)

AF:

0.349

AC:

15617

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.297

AC:

7764

AN:

26136

East Asian (EAS)

AF:

0.353

AC:

14017

AN:

39698

South Asian (SAS)

AF:

0.301

AC:

25939

AN:

86258

European-Finnish (FIN)

AF:

0.391

AC:

20847

AN:

53356

Middle Eastern (MID)

AF:

0.338

AC:

1948

AN:

5768

European-Non Finnish (NFE)

AF:

0.379

AC:

421706

AN:

1111974

Other (OTH)

AF:

0.367

AC:

22164

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

24122

48244

72367

96489

120611

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13312

26624

39936

53248

66560

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.378

AC:

57378

AN:

151922

Hom.:

10949

Cov.:

AF XY:

0.381

AC XY:

28276

AN XY:

74228

show subpopulations

African (AFR)

AF:

0.396

AC:

16419

AN:

41436

American (AMR)

AF:

0.369

AC:

5627

AN:

15244

Ashkenazi Jewish (ASJ)

AF:

0.291

AC:

1007

AN:

3466

East Asian (EAS)

AF:

0.351

AC:

1809

AN:

5158

South Asian (SAS)

AF:

0.301

AC:

1449

AN:

4818

European-Finnish (FIN)

AF:

0.396

AC:

4179

AN:

10552

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.377

AC:

25588

AN:

67946

Other (OTH)

AF:

0.387

AC:

814

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1808

3616

5425

7233

9041

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

548

1096

1644

2192

2740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.5

(source)

DANN

Benign

0.71

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0025

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.4

M;M

PhyloP100

0.096

PrimateAI

Benign

0.28

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

GERP RS

-1.1

Varity_R

0.20

gMVP

0.70

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over