dbSNP rs182152963: PXDN:c.1018+9C>T (chr2-1673634-G-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_012293.3(PXDN):c.1018+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00091 in 1,598,472 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0037 ( 7 hom., cov: 33)

Exomes 𝑓: 0.00061 ( 5 hom. )

Consequence

PXDN
NM_012293.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.307

Publications

0 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 2-1673634-G-A is Benign according to our data. Variant chr2-1673634-G-A is described in ClinVar as Benign. ClinVar VariationId is 471909.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00374 (570/152282) while in subpopulation AFR AF = 0.0128 (533/41536). AF 95% confidence interval is 0.0119. There are 7 homozygotes in GnomAd4. There are 292 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PXDN	NM_012293.3 link	c.1018+9C>T		intron_variant	Intron 9 of 22	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9 link	c.1018+9C>T		intron_variant	Intron 9 of 22	1	NM_012293.3	ENSP00000252804.4

Frequencies

GnomAD3 genomes

AF:

0.00370

AC:

563

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0127

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00383

GnomAD2 exomes

AF:

0.00108

AC:

266

AN:

245580

AF XY:

0.000954

show subpopulations

Gnomad AFR exome

AF:

0.0153

Gnomad AMR exome

AF:

0.000207

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000180

Gnomad OTH exome

AF:

0.000505

GnomAD4 exome

AF:

0.000611

AC:

884

AN:

1446190

Hom.:

Cov.:

AF XY:

0.000543

AC XY:

389

AN XY:

717040

show subpopulations

African (AFR)

AF:

0.0167

AC:

554

AN:

33224

American (AMR)

AF:

0.000248

AC:

AN:

44296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25750

East Asian (EAS)

AF:

0.00

AC:

AN:

39340

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84660

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53142

Middle Eastern (MID)

AF:

0.00140

AC:

AN:

5700

European-Non Finnish (NFE)

AF:

0.000238

AC:

262

AN:

1100496

Other (OTH)

AF:

0.000806

AC:

AN:

59582

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

135

180

225

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

<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:

0.00374

AC:

570

AN:

152282

Hom.:

Cov.:

AF XY:

0.00392

AC XY:

292

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0128

AC:

533

AN:

41536

American (AMR)

AF:

0.00163

AC:

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68028

Other (OTH)

AF:

0.00379

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

103

129

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00211

Hom.:

Bravo

AF:

0.00445

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Anterior segment dysgenesis 7

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

7.7

(source)

DANN

Benign

0.66

PhyloP100

0.31

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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