2-1635241-C-T

Position:

• chr2-1635241-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012293.3(PXDN):​c.4320+167G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0697 in 152,258 control chromosomes in the GnomAD database, including 411 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.070 (411 hom., cov: 33)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.12

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 2-1635241-C-T is Benign according to our data. Variant chr2-1635241-C-T is described in ClinVar as [Benign]. Clinvar id is 1181085.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3	c.4320+167G>A		intron_variant		ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.4320+167G>A		intron_variant		1	NM_012293.3	ENSP00000252804.4
PXDN	ENST00000453308.1	n.*110+167G>A		intron_variant		3		ENSP00000414098.1
PXDN	ENST00000478155.5	n.3408+167G>A		intron_variant		2
PXDN	ENST00000493654.1	n.1657+167G>A		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0697 AC: 10605 AN: 152140 Hom.: 410 Cov.: 33

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.0592

Gnomad AMR AF: 0.0799

Gnomad ASJ AF: 0.0643

Gnomad EAS AF: 0.00812

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0585

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0844

Gnomad OTH AF: 0.0651

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0697 AC: 10614 AN: 152258 Hom.: 411 Cov.: 33 AF XY: 0.0675 AC XY: 5025 AN XY: 74434

Gnomad4 AFR AF: 0.0596

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.0643

Gnomad4 EAS AF: 0.00814

Gnomad4 SAS AF: 0.0178

Gnomad4 FIN AF: 0.0585

Gnomad4 NFE AF: 0.0844

Gnomad4 OTH AF: 0.0649

Alfa AF: 0.0830 Hom.: 96

Bravo AF: 0.0693

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

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

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.6
DANN	Benign	0.73

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

Other links and lift over

dbSNP: rs7602869; hg19: chr2-1639013;