2-1643399-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012293.3(PXDN):c.3921A>G(p.Val1307Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.896 in 1,613,732 control chromosomes in the GnomAD database, including 648,234 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.87 ( 58332 hom., cov: 33)

Exomes 𝑓: 0.90 ( 589902 hom. )

Consequence

PXDN
NM_012293.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.519

Publications

21 publications found

Variant links:

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)

PXDN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 2-1643399-T-C is Benign according to our data. Variant chr2-1643399-T-C is described in ClinVar as [Benign]. Clinvar id is 260228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.519 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDN	NM_012293.3 link	c.3921A>G	p.Val1307Val	synonymous_variant	Exon 19 of 23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PXDN	ENST00000252804.9 link	c.3921A>G	p.Val1307Val	synonymous_variant	Exon 19 of 23	1	NM_012293.3	ENSP00000252804.4	Q92626-1
PXDN	ENST00000453308.1 link	n.72A>G		non_coding_transcript_exon_variant	Exon 1 of 4	3		ENSP00000414098.1	H7C3W2
PXDN	ENST00000477093.1 link	n.563A>G		non_coding_transcript_exon_variant	Exon 3 of 3	4
PXDN	ENST00000478155.5 link	n.3009A>G		non_coding_transcript_exon_variant	Exon 11 of 15	2

Frequencies

GnomAD3 genomes

AF:

0.874

AC:

132849

AN:

152082

Hom.:

58289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.792

Gnomad AMI

AF:

0.914

Gnomad AMR

AF:

0.929

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.974

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.956

Gnomad NFE

AF:

0.889

Gnomad OTH

AF:

0.877

GnomAD2 exomes

AF:

0.913

AC:

227130

AN:

248898

AF XY:

0.915

show subpopulations

Gnomad AFR exome

AF:

0.790

Gnomad AMR exome

AF:

0.953

Gnomad ASJ exome

AF:

0.895

Gnomad EAS exome

AF:

1.00

Gnomad FIN exome

AF:

0.887

Gnomad NFE exome

AF:

0.893

Gnomad OTH exome

AF:

0.912

GnomAD4 exome

AF:

0.898

AC:

1312187

AN:

1461532

Hom.:

589902

Cov.:

AF XY:

0.900

AC XY:

654521

AN XY:

727056

show subpopulations

African (AFR)

AF:

0.791

AC:

26482

AN:

33476

American (AMR)

AF:

0.951

AC:

42517

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.895

AC:

23385

AN:

26136

East Asian (EAS)

AF:

1.00

AC:

39694

AN:

39700

South Asian (SAS)

AF:

0.971

AC:

83730

AN:

86256

European-Finnish (FIN)

AF:

0.883

AC:

47013

AN:

53252

Middle Eastern (MID)

AF:

0.951

AC:

5484

AN:

5766

European-Non Finnish (NFE)

AF:

0.890

AC:

989372

AN:

1111852

Other (OTH)

AF:

0.903

AC:

54510

AN:

60370

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

7767

15533

23300

31066

38833

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21410

42820

64230

85640

107050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.874

AC:

132949

AN:

152200

Hom.:

58332

Cov.:

AF XY:

0.878

AC XY:

65304

AN XY:

74392

show subpopulations

African (AFR)

AF:

0.792

AC:

32869

AN:

41514

American (AMR)

AF:

0.929

AC:

14217

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.901

AC:

3129

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5158

AN:

5164

South Asian (SAS)

AF:

0.974

AC:

4691

AN:

4816

European-Finnish (FIN)

AF:

0.889

AC:

9421

AN:

10600

Middle Eastern (MID)

AF:

0.956

AC:

281

AN:

294

European-Non Finnish (NFE)

AF:

0.889

AC:

60493

AN:

68018

Other (OTH)

AF:

0.879

AC:

1856

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

864

1727

2591

3454

4318

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

898

1796

2694

3592

4490

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.887

Hom.:

93945

Bravo

AF:

0.872

Asia WGS

AF:

0.977

AC:

3395

AN:

3478

EpiCase

AF:

0.896

EpiControl

AF:

0.898

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Anterior segment dysgenesis 7

Benign:2

Jul 14, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 24, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

6.7

(source)

DANN

Benign

0.48

PhyloP100

0.52

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over