rs7588627

chr2-1662203-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012293.3(PXDN):c.1568-19C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0199 in 1,556,176 control chromosomes in the GnomAD database, including 2,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.075 (1157 hom., cov: 33)
  • Exomes 𝑓: 0.014 (1330 hom.)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.382

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-1662203-G-C is Benign according to our data. Variant chr2-1662203-G-C is described in ClinVar as [Benign]. Clinvar id is 260219.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDN	NM_012293.3	c.1568-19C>G		intron_variant		ENST00000252804.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDN	ENST00000252804.9	c.1568-19C>G		intron_variant		1	NM_012293.3	P1
PXDN	ENST00000433670.5	c.1555-19C>G		intron_variant		1
PXDN	ENST00000425171.2	c.1496-19C>G		intron_variant		5
PXDN	ENST00000478155.5	n.2160-19C>G		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0747 AC: 11372 AN: 152168 Hom.: 1154 Cov.: 33

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0277

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0101

Gnomad FIN AF: 0.0412

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.00294

Gnomad OTH AF: 0.0554

GnomAD3 exomes AF: 0.0319 AC: 5540 AN: 173914 Hom.: 378 AF XY: 0.0274 AC XY: 2533 AN XY: 92482

Gnomad AFR exome AF: 0.235

Gnomad AMR exome AF: 0.0136

Gnomad ASJ exome AF: 0.0102

Gnomad EAS exome AF: 0.125

Gnomad SAS exome AF: 0.00607

Gnomad FIN exome AF: 0.0430

Gnomad NFE exome AF: 0.00306

Gnomad OTH exome AF: 0.0248

GnomAD4 exome AF: 0.0139 AC: 19562 AN: 1403890 Hom.: 1330 Cov.: 28 AF XY: 0.0130 AC XY: 9023 AN XY: 694528

Gnomad4 AFR exome AF: 0.241

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0118

Gnomad4 EAS exome AF: 0.107

Gnomad4 SAS exome AF: 0.00714

Gnomad4 FIN exome AF: 0.0404

Gnomad4 NFE exome AF: 0.00230

Gnomad4 OTH exome AF: 0.0296

GnomAD4 genome AF: 0.0748 AC: 11392 AN: 152286 Hom.: 1157 Cov.: 33 AF XY: 0.0742 AC XY: 5529 AN XY: 74472

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0276

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.125

Gnomad4 SAS AF: 0.00973

Gnomad4 FIN AF: 0.0412

Gnomad4 NFE AF: 0.00293

Gnomad4 OTH AF: 0.0558

Alfa AF: 0.0344 Hom.: 73

Bravo AF: 0.0813

Asia WGS AF: 0.0860 AC: 298 AN: 3478

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 31, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.45
Dann	Benign	0.29

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs7588627; hg19: chr2-1665975;