Variant 2-1634446-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_012293.3(PXDN):c.4321-123C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00283 in 1,250,356 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.014 ( 43 hom., cov: 33)

Exomes 𝑓: 0.0013 ( 38 hom. )

Consequence

PXDN
NM_012293.3 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.06

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 2-1634446-G-C is Benign according to our data. Variant chr2-1634446-G-C is described in ClinVar as [Benign]. Clinvar id is 1182742.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2105/152360) while in subpopulation AFR AF= 0.0473 (1966/41590). AF 95% confidence interval is 0.0455. There are 43 homozygotes in gnomad4. There are 1005 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 43 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3 linkuse as main transcript	c.4321-123C>G		intron_variant		ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
PXDN	ENST00000252804.9 linkuse as main transcript	c.4321-123C>G	intron_variant	1	NM_012293.3	ENSP00000252804.4	Q92626-1
PXDN	ENST00000453308.1 linkuse as main transcript	n.*111-123C>G	intron_variant	3		ENSP00000414098.1	H7C3W2
PXDN	ENST00000478155.5 linkuse as main transcript	n.3409-123C>G	intron_variant	2
PXDN	ENST00000493654.1 linkuse as main transcript	n.1658-123C>G	intron_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0138

AC:

2101

AN:

152242

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0473

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00608

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.0148

GnomAD4 exome

AF:

0.00131

AC:

1434

AN:

1097996

Hom.:

AF XY:

0.00117

AC XY:

632

AN XY:

537896

show subpopulations

Gnomad4 AFR exome

AF:

0.0464

Gnomad4 AMR exome

AF:

0.00405

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000109

Gnomad4 FIN exome

AF:

0.0000234

Gnomad4 NFE exome

AF:

0.0000738

Gnomad4 OTH exome

AF:

0.00298

GnomAD4 genome

AF:

0.0138

AC:

2105

AN:

152360

Hom.:

Cov.:

AF XY:

0.0135

AC XY:

1005

AN XY:

74506

show subpopulations

Gnomad4 AFR

AF:

0.0473

Gnomad4 AMR

AF:

0.00608

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.0147

Alfa

AF:

0.0113

Hom.:

Bravo

AF:

0.0154

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.60

DANN

Benign

0.45

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