2-1639436-A-G

Variant names:

• chr2-1639436-A-G
• rs7578605
• NM_012293.3:c.3953-14T>C

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.3953-14T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0641 in 1,613,794 control chromosomes in the GnomAD database, including 3,997 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.087 (726 hom., cov: 33)
  • Exomes 𝑓: 0.062 (3271 hom.)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.144
• Publications: 10 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=-0.73).
• BP6: Variant 2-1639436-A-G is Benign according to our data. Variant chr2-1639436-A-G is described in ClinVar as Benign. ClinVar VariationId is 260229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	NM_012293.3	MANE Select	c.3953-14T>C		intron	N/A	NP_036425.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	ENST00000252804.9	TSL:1 MANE Select	c.3953-14T>C		intron	N/A	ENSP00000252804.4
	PXDN	ENST00000453308.1	TSL:3	n.104-14T>C		intron	N/A	ENSP00000414098.1
	PXDN	ENST00000478155.5	TSL:2	n.3041-14T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0874 AC: 13298 AN: 152188 Hom.: 721 Cov.: 33

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.0208

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0421

Gnomad EAS AF: 0.00789

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.0503

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0673

Gnomad OTH AF: 0.0847

GnomAD2 exomes AF: 0.0608 AC: 15140 AN: 249136 AF XY: 0.0559

Gnomad AFR exome AF: 0.158

Gnomad AMR exome AF: 0.0872

Gnomad ASJ exome AF: 0.0419

Gnomad EAS exome AF: 0.00606

Gnomad FIN exome AF: 0.0497

Gnomad NFE exome AF: 0.0641

Gnomad OTH exome AF: 0.0622

GnomAD4 exome AF: 0.0617 AC: 90166 AN: 1461488 Hom.: 3271 Cov.: 33 AF XY: 0.0598 AC XY: 43505 AN XY: 727030

African (AFR) AF: 0.156 AC: 5204 AN: 33464

American (AMR) AF: 0.0910 AC: 4069 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 1119 AN: 26128

East Asian (EAS) AF: 0.00282 AC: 112 AN: 39700

South Asian (SAS) AF: 0.0154 AC: 1324 AN: 86250

European-Finnish (FIN) AF: 0.0520 AC: 2778 AN: 53390

Middle Eastern (MID) AF: 0.0279 AC: 161 AN: 5762

European-Non Finnish (NFE) AF: 0.0645 AC: 71742 AN: 1111724

Other (OTH) AF: 0.0606 AC: 3657 AN: 60358

GnomAD4 genome AF: 0.0875 AC: 13326 AN: 152306 Hom.: 726 Cov.: 33 AF XY: 0.0851 AC XY: 6341 AN XY: 74478

African (AFR) AF: 0.154 AC: 6402 AN: 41554

American (AMR) AF: 0.0875 AC: 1340 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0421 AC: 146 AN: 3472

East Asian (EAS) AF: 0.00791 AC: 41 AN: 5184

South Asian (SAS) AF: 0.0157 AC: 76 AN: 4832

European-Finnish (FIN) AF: 0.0503 AC: 534 AN: 10614

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0673 AC: 4579 AN: 68024

Other (OTH) AF: 0.0843 AC: 178 AN: 2112

Alfa AF: 0.0722 Hom.: 1877

Bravo AF: 0.0919

Asia WGS AF: 0.0290 AC: 103 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Anterior segment dysgenesis 7 Benign:2

Jan 29, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Nov 07, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Aug 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.39
DANN	Benign	0.63
PhyloP100		-0.14
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: rs7578605; hg19: chr2-1643208;