Variant chr2-1639436-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.144

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 links:

PXDN (HGNC:):

PXDN links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 260229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-1639436-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.151 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3 linkuse as main transcript	c.3953-14T>C		intron_variant		ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.3953-14T>C	intron_variant	1	NM_012293.3	ENSP00000252804.4	Q92626-1
PXDN	ENST00000453308.1 linkuse as main transcript	n.104-14T>C	intron_variant	3		ENSP00000414098.1	H7C3W2
PXDN	ENST00000478155.5 linkuse as main transcript	n.3041-14T>C	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0874

AC:

13298

AN:

152188

Hom.:

721

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.0608

AC:

15140

AN:

249136

Hom.:

621

AF XY:

0.0559

AC XY:

7559

AN XY:

135156

show subpopulations

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 SAS exome

AF:

0.0154

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.:

AF XY:

0.0598

AC XY:

43505

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.156

Gnomad4 AMR exome

AF:

0.0910

Gnomad4 ASJ exome

AF:

0.0428

Gnomad4 EAS exome

AF:

0.00282

Gnomad4 SAS exome

AF:

0.0154

Gnomad4 FIN exome

AF:

0.0520

Gnomad4 NFE exome

AF:

0.0645

Gnomad4 OTH exome

AF:

0.0606

GnomAD4 genome

AF:

0.0875

AC:

13326

AN:

152306

Hom.:

726

Cov.:

AF XY:

0.0851

AC XY:

6341

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.154

Gnomad4 AMR

AF:

0.0875

Gnomad4 ASJ

AF:

0.0421

Gnomad4 EAS

AF:

0.00791

Gnomad4 SAS

AF:

0.0157

Gnomad4 FIN

AF:

0.0503

Gnomad4 NFE

AF:

0.0673

Gnomad4 OTH

AF:

0.0843

Alfa

AF:

0.0671

Hom.:

738

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

LINK: link

Submissions by phenotype

Anterior segment dysgenesis 7

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Nov 07, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

0.39

DANN

Benign

0.63

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over