chr2-1649050-T-G

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.2730A>C(p.Ile910Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.9 in 1,612,596 control chromosomes in the GnomAD database, including 653,976 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.90 ( 61394 hom., cov: 32)

Exomes 𝑓: 0.90 ( 592582 hom. )

Consequence

PXDN
NM_012293.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.196

Publications

22 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=-0.54).

BP6

Variant 2-1649050-T-G is Benign according to our data. Variant chr2-1649050-T-G is described in ClinVar as Benign. ClinVar VariationId is 260223.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.196 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.2730A>C	p.Ile910Ile	synonymous	Exon 17 of 23	NP_036425.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
PXDN	ENST00000252804.9	TSL:1 MANE Select	c.2730A>C	p.Ile910Ile	synonymous	Exon 17 of 23	ENSP00000252804.4
PXDN	ENST00000478155.5	TSL:2	n.2697-4298A>C		intron	N/A
PXDN	ENST00000493779.1	TSL:2	n.*193A>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.898

AC:

136476

AN:

152028

Hom.:

61337

Cov.:

show subpopulations

Gnomad AFR

AF:

0.875

Gnomad AMI

AF:

0.914

Gnomad AMR

AF:

0.938

Gnomad ASJ

AF:

0.901

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.975

Gnomad FIN

AF:

0.889

Gnomad MID

AF:

0.965

Gnomad NFE

AF:

0.890

Gnomad OTH

AF:

0.902

GnomAD2 exomes

AF:

0.919

AC:

224653

AN:

244392

AF XY:

0.920

show subpopulations

Gnomad AFR exome

AF:

0.878

Gnomad AMR exome

AF:

0.958

Gnomad ASJ exome

AF:

0.894

Gnomad EAS exome

AF:

0.999

Gnomad FIN exome

AF:

0.888

Gnomad NFE exome

AF:

0.894

Gnomad OTH exome

AF:

0.916

GnomAD4 exome

AF:

0.900

AC:

1314859

AN:

1460450

Hom.:

592582

Cov.:

AF XY:

0.902

AC XY:

655595

AN XY:

726536

show subpopulations

African (AFR)

AF:

0.875

AC:

29290

AN:

33480

American (AMR)

AF:

0.956

AC:

42746

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.894

AC:

23366

AN:

26128

East Asian (EAS)

AF:

1.00

AC:

39679

AN:

39696

South Asian (SAS)

AF:

0.970

AC:

83629

AN:

86258

European-Finnish (FIN)

AF:

0.884

AC:

46163

AN:

52232

Middle Eastern (MID)

AF:

0.956

AC:

5515

AN:

5768

European-Non Finnish (NFE)

AF:

0.890

AC:

989643

AN:

1111810

Other (OTH)

AF:

0.908

AC:

54828

AN:

60356

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

9322

18644

27965

37287

46609

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21416

42832

64248

85664

107080

<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:

0.898

AC:

136592

AN:

152146

Hom.:

61394

Cov.:

AF XY:

0.901

AC XY:

67018

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.876

AC:

36363

AN:

41528

American (AMR)

AF:

0.938

AC:

14356

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.901

AC:

3130

AN:

3472

East Asian (EAS)

AF:

0.998

AC:

5098

AN:

5110

South Asian (SAS)

AF:

0.974

AC:

4699

AN:

4822

European-Finnish (FIN)

AF:

0.889

AC:

9430

AN:

10606

Middle Eastern (MID)

AF:

0.966

AC:

284

AN:

294

European-Non Finnish (NFE)

AF:

0.890

AC:

60489

AN:

67984

Other (OTH)

AF:

0.904

AC:

1909

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

707

1414

2120

2827

3534

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<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:

0.894

Hom.:

94925

Bravo

AF:

0.900

Asia WGS

AF:

0.980

AC:

3406

AN:

3478

EpiCase

AF:

0.896

EpiControl

AF:

0.899

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

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Jul 14, 2021

Genome-Nilou Lab

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 v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.2

(source)

DANN

Benign

0.75

PhyloP100

-0.20

Mutation Taster

=96/4

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over