2-1660882-A-G

Position:

• chr2-1660882-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_012293.3(PXDN):​c.1836T>C​(p.Asn612Asn) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.721 in 1,608,282 control chromosomes in the GnomAD database, including 420,966 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.72 (40055 hom., cov: 32)
  • Exomes 𝑓: 0.72 (380911 hom.)
• Consequence: PXDN NM_012293.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00001360
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.188

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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-1660882-A-G is Benign according to our data. Variant chr2-1660882-A-G is described in ClinVar as [Benign]. Clinvar id is 260220.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.188 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.955 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3	c.1836T>C	p.Asn612Asn	splice_region_variant, synonymous_variant	14/23	ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.1836T>C	p.Asn612Asn	splice_region_variant, synonymous_variant	14/23	1	NM_012293.3	ENSP00000252804.4
PXDN	ENST00000433670.5	c.1821T>C	p.Asn607Asn	splice_region_variant, synonymous_variant	14/16	1		ENSP00000402738.1
PXDN	ENST00000425171.2	c.1764T>C	p.Asn588Asn	splice_region_variant, synonymous_variant	13/16	5		ENSP00000398363.2
PXDN	ENST00000478155.5	n.2428T>C		splice_region_variant, non_coding_transcript_exon_variant	7/15	2

Frequencies

GnomAD3 genomes AF: 0.723 AC: 109941 AN: 151958 Hom.: 40025 Cov.: 32

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.754

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.978

Gnomad SAS AF: 0.859

Gnomad FIN AF: 0.676

Gnomad MID AF: 0.668

Gnomad NFE AF: 0.694

Gnomad OTH AF: 0.709

GnomAD3 exomes AF: 0.756 AC: 187436 AN: 247928 Hom.: 72174 AF XY: 0.755 AC XY: 101438 AN XY: 134438

Gnomad AFR exome AF: 0.725

Gnomad AMR exome AF: 0.837

Gnomad ASJ exome AF: 0.693

Gnomad EAS exome AF: 0.982

Gnomad SAS exome AF: 0.855

Gnomad FIN exome AF: 0.682

Gnomad NFE exome AF: 0.694

Gnomad OTH exome AF: 0.722

GnomAD4 exome AF: 0.720 AC: 1048822 AN: 1456206 Hom.: 380911 Cov.: 56 AF XY: 0.724 AC XY: 523458 AN XY: 723404

Gnomad4 AFR exome AF: 0.732

Gnomad4 AMR exome AF: 0.828

Gnomad4 ASJ exome AF: 0.695

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.855

Gnomad4 FIN exome AF: 0.680

Gnomad4 NFE exome AF: 0.698

Gnomad4 OTH exome AF: 0.730

GnomAD4 genome AF: 0.724 AC: 110029 AN: 152076 Hom.: 40055 Cov.: 32 AF XY: 0.727 AC XY: 54062 AN XY: 74332

Gnomad4 AFR AF: 0.729

Gnomad4 AMR AF: 0.754

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.977

Gnomad4 SAS AF: 0.858

Gnomad4 FIN AF: 0.676

Gnomad4 NFE AF: 0.694

Gnomad4 OTH AF: 0.714

Alfa AF: 0.698 Hom.: 45328

Bravo AF: 0.729

Asia WGS AF: 0.889 AC: 3093 AN: 3478

EpiCase AF: 0.687

EpiControl AF: 0.683

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Anterior segment dysgenesis 7 Benign:2

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

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.081
DANN	Benign	0.62

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000014
dbscSNV1_RF	Benign	0.0
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: rs17841813; hg19: chr2-1664654;