rs7588627

Variant names:

• chr2-1662203-G-C
• rs7588627
• NM_012293.3:c.1568-19C>G

Variant summary

Our verdict is Benign. The variant received -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:4
• Conservation: PhyloP100: -0.382
• Publications: 3 publications found

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]

PXDN Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, PanelApp Australia, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
PXDN	NM_012293.3	c.1568-19C>G		intron_variant	Intron 12 of 22	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.1568-19C>G		intron_variant	Intron 12 of 22	1	NM_012293.3	ENSP00000252804.4
PXDN	ENST00000433670.5	c.1553-19C>G		intron_variant	Intron 12 of 15	1		ENSP00000402738.1
PXDN	ENST00000425171.2	c.1496-19C>G		intron_variant	Intron 11 of 15	5		ENSP00000398363.2
PXDN	ENST00000478155.5	n.2160-19C>G		intron_variant	Intron 5 of 14	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

GnomAD2 exomes AF: 0.0319 AC: 5540 AN: 173914 AF XY: 0.0274

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 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

African (AFR) AF: 0.241 AC: 7772 AN: 32212

American (AMR) AF: 0.0148 AC: 552 AN: 37236

Ashkenazi Jewish (ASJ) AF: 0.0118 AC: 297 AN: 25248

East Asian (EAS) AF: 0.107 AC: 3999 AN: 37234

South Asian (SAS) AF: 0.00714 AC: 572 AN: 80142

European-Finnish (FIN) AF: 0.0404 AC: 2042 AN: 50506

Middle Eastern (MID) AF: 0.0216 AC: 123 AN: 5702

European-Non Finnish (NFE) AF: 0.00230 AC: 2479 AN: 1077220

Other (OTH) AF: 0.0296 AC: 1726 AN: 58390

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

African (AFR) AF: 0.228 AC: 9475 AN: 41528

American (AMR) AF: 0.0276 AC: 423 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3468

East Asian (EAS) AF: 0.125 AC: 645 AN: 5176

South Asian (SAS) AF: 0.00973 AC: 47 AN: 4828

European-Finnish (FIN) AF: 0.0412 AC: 438 AN: 10632

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.00293 AC: 199 AN: 68030

Other (OTH) AF: 0.0558 AC: 118 AN: 2114

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Sep 18, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Anterior segment dysgenesis 7 Benign:1

Jan 17, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.45
DANN	Benign	0.29
PhyloP100		-0.38
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7588627; hg19: chr2-1665975;