rs1863134

chr2-1649119-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_012293.3(PXDN):c.2661C>T(p.Ser887=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00865 in 1,612,636 control chromosomes in the GnomAD database, including 905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.044 (463 hom., cov: 32)
  • Exomes 𝑓: 0.0050 (442 hom.)
• Consequence: PXDN NM_012293.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0520

Genes affected

PXDN (HGNC:14966): (peroxidasin) This gene encodes a heme-containing peroxidase that is secreted into the extracellular matrix. It is involved in extracellular matrix formation, and may function in the physiological and pathological fibrogenic response in fibrotic kidney. Mutations in this gene cause corneal opacification and other ocular anomalies, and also microphthalmia and anterior segment dysgenesis. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.41).
• BP6: Variant 2-1649119-G-A is Benign according to our data. Variant chr2-1649119-G-A is described in ClinVar as [Benign]. Clinvar id is 260222.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.052 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDN	NM_012293.3	c.2661C>T	p.Ser887=	synonymous_variant	17/23	ENST00000252804.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDN	ENST00000252804.9	c.2661C>T	p.Ser887=	synonymous_variant	17/23	1	NM_012293.3	P1
PXDN	ENST00000478155.5	n.2697-4367C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0439 AC: 6674 AN: 151986 Hom.: 462 Cov.: 32

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0170

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00814

Gnomad SAS AF: 0.00601

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.0450

GnomAD3 exomes AF: 0.0120 AC: 2947 AN: 245288 Hom.: 197 AF XY: 0.00968 AC XY: 1297 AN XY: 133972

Gnomad AFR exome AF: 0.160

Gnomad AMR exome AF: 0.00747

Gnomad ASJ exome AF: 0.000503

Gnomad EAS exome AF: 0.00598

Gnomad SAS exome AF: 0.00462

Gnomad FIN exome AF: 0.0000466

Gnomad NFE exome AF: 0.000408

Gnomad OTH exome AF: 0.00752

GnomAD4 exome AF: 0.00496 AC: 7251 AN: 1460532 Hom.: 442 Cov.: 86 AF XY: 0.00444 AC XY: 3227 AN XY: 726552

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.00868

Gnomad4 ASJ exome AF: 0.000153

Gnomad4 EAS exome AF: 0.00237

Gnomad4 SAS exome AF: 0.00424

Gnomad4 FIN exome AF: 0.0000382

Gnomad4 NFE exome AF: 0.000360

Gnomad4 OTH exome AF: 0.0110

GnomAD4 genome AF: 0.0440 AC: 6695 AN: 152104 Hom.: 463 Cov.: 32 AF XY: 0.0427 AC XY: 3176 AN XY: 74346

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0169

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.00816

Gnomad4 SAS AF: 0.00602

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.0450

Alfa AF: 0.0201 Hom.: 98

Bravo AF: 0.0497

Asia WGS AF: 0.0180 AC: 63 AN: 3478

EpiCase AF: 0.000436

EpiControl AF: 0.000711

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Anterior segment dysgenesis 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 22, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 31, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	8.6
Dann	Benign	0.80

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: rs1863134; hg19: chr2-1652891;