Variant chr2-1649050-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_012293.3(PXDN):c.2730A>C(p.Ile910=) 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

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDN	NM_012293.3 linkuse as main transcript	c.2730A>C	p.Ile910=	synonymous_variant	17/23	ENST00000252804.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.2730A>C	p.Ile910=	synonymous_variant	17/23	1	NM_012293.3	P1	Q92626-1
PXDN	ENST00000478155.5 linkuse as main transcript	n.2697-4298A>C		intron_variant, non_coding_transcript_variant		2

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

GnomAD3 exomes

AF:

0.919

AC:

224653

AN:

244392

Hom.:

103437

AF XY:

0.920

AC XY:

123018

AN XY:

133736

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 SAS exome

AF:

0.971

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

Gnomad4 AFR exome

AF:

0.875

Gnomad4 AMR exome

AF:

0.956

Gnomad4 ASJ exome

AF:

0.894

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.970

Gnomad4 FIN exome

AF:

0.884

Gnomad4 NFE exome

AF:

0.890

Gnomad4 OTH exome

AF:

0.908

GnomAD4 genome

AF:

0.898

AC:

136592

AN:

152146

Hom.:

61394

Cov.:

AF XY:

0.901

AC XY:

67018

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.876

Gnomad4 AMR

AF:

0.938

Gnomad4 ASJ

AF:

0.901

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.974

Gnomad4 FIN

AF:

0.889

Gnomad4 NFE

AF:

0.890

Gnomad4 OTH

AF:

0.904

Alfa

AF:

0.893

Hom.:

76844

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

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 24, 2018	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. -

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

-0.54

CADD

Benign

4.2

DANN

Benign

0.75

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

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