19-15475969-C-A

Position:

• chr19-15475969-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_052890.4(PGLYRP2):​c.701G>T​(p.Gly234Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,138 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0080 (13 hom., cov: 32)
  • Exomes 𝑓: 0.00091 (18 hom.)
• Consequence: PGLYRP2 NM_052890.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.779

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004096508).
• BP6: Variant 19-15475969-C-A is Benign according to our data. Variant chr19-15475969-C-A is described in ClinVar as [Benign]. Clinvar id is 720778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00801 (1219/152262) while in subpopulation AFR AF= 0.0274 (1138/41550). AF 95% confidence interval is 0.0261. There are 13 homozygotes in gnomad4. There are 578 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 13 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGLYRP2	NM_052890.4	c.701G>T	p.Gly234Val	missense_variant	2/5	ENST00000340880.5	NP_443122.3
PGLYRP2	NM_001363546.1	c.701G>T	p.Gly234Val	missense_variant	2/4		NP_001350475.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGLYRP2	ENST00000340880.5	c.701G>T	p.Gly234Val	missense_variant	2/5	1	NM_052890.4	ENSP00000345968	P2
PGLYRP2	ENST00000292609.8	c.701G>T	p.Gly234Val	missense_variant	2/4	1		ENSP00000292609	A2

Frequencies

GnomAD3 genomes AF: 0.00802 AC: 1220 AN: 152144 Hom.: 13 Cov.: 32

Gnomad AFR AF: 0.0275

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00236

Gnomad ASJ AF: 0.00720

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00622

GnomAD3 exomes AF: 0.00231 AC: 580 AN: 251354 Hom.: 10 AF XY: 0.00174 AC XY: 236 AN XY: 135878

Gnomad AFR exome AF: 0.0288

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000968

Gnomad OTH exome AF: 0.000815

GnomAD4 exome AF: 0.000906 AC: 1324 AN: 1461876 Hom.: 18 Cov.: 72 AF XY: 0.000806 AC XY: 586 AN XY: 727238

Gnomad4 AFR exome AF: 0.0271

Gnomad4 AMR exome AF: 0.00110

Gnomad4 ASJ exome AF: 0.00681

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000580

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000369

Gnomad4 OTH exome AF: 0.00227

GnomAD4 genome AF: 0.00801 AC: 1219 AN: 152262 Hom.: 13 Cov.: 32 AF XY: 0.00776 AC XY: 578 AN XY: 74452

Gnomad4 AFR AF: 0.0274

Gnomad4 AMR AF: 0.00235

Gnomad4 ASJ AF: 0.00720

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00616

Alfa AF: 0.00166 Hom.: 4

Bravo AF: 0.00878

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00 AC: 0

ESP6500AA AF: 0.0268 AC: 118

ESP6500EA AF: 0.000581 AC: 5

ExAC AF: 0.00264 AC: 321

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 29, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.74	T
BayesDel_noAF	Benign	-0.81
CADD	Benign	0.14
DANN	Benign	0.14
DEOGEN2	Benign	0.074	.;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.063	N
LIST_S2	Benign	0.69	T;T
MetaRNN	Benign	0.0041	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.4	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.021
Sift	Benign	0.45	T;T
Sift4G	Benign	0.42	T;T
Polyphen		0.12	B;B
Vest4		0.097
MVP		0.32
MPC		0.20
ClinPred		0.0044	T
GERP RS		-1.5
Varity_R		0.036
gMVP		0.52

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: rs144572782; hg19: chr19-15586780; COSMIC: COSV99035213; COSMIC: COSV99035213;