rs73178792

chr2-1654394-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.1946+6G>A variant causes a splice donor region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0108 in 1,606,026 control chromosomes in the GnomAD database, including 1,260 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.054 (656 hom., cov: 33)
  • Exomes 𝑓: 0.0063 (604 hom.)
• Consequence: PXDN NM_012293.3 splice_donor_region, intron
• Scores: Splicing: ADA: 0.00003743
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.723

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 2-1654394-C-T is Benign according to our data. Variant chr2-1654394-C-T is described in ClinVar as [Benign]. Clinvar id is 260221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.179 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
PXDN	NM_012293.3	c.1946+6G>A		splice_donor_region_variant, intron_variant		ENST00000252804.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
PXDN	ENST00000252804.9	c.1946+6G>A		splice_donor_region_variant, intron_variant		1	NM_012293.3	P1
PXDN	ENST00000433670.5	c.1933+6G>A		splice_donor_region_variant, intron_variant		1
PXDN	ENST00000425171.2	c.1874+6G>A		splice_donor_region_variant, intron_variant		5
PXDN	ENST00000478155.5	n.2538+6G>A		splice_donor_region_variant, intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0536 AC: 8151 AN: 152142 Hom.: 656 Cov.: 33

Gnomad AFR AF: 0.182

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0208

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.00788

Gnomad SAS AF: 0.00622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.000926

Gnomad OTH AF: 0.0545

GnomAD3 exomes AF: 0.0149 AC: 3714 AN: 249004 Hom.: 296 AF XY: 0.0114 AC XY: 1546 AN XY: 135102

Gnomad AFR exome AF: 0.184

Gnomad AMR exome AF: 0.0101

Gnomad ASJ exome AF: 0.00995

Gnomad EAS exome AF: 0.00607

Gnomad SAS exome AF: 0.00458

Gnomad FIN exome AF: 0.0000928

Gnomad NFE exome AF: 0.000930

Gnomad OTH exome AF: 0.00976

GnomAD4 exome AF: 0.00629 AC: 9150 AN: 1453766 Hom.: 604 Cov.: 30 AF XY: 0.00550 AC XY: 3982 AN XY: 723414

Gnomad4 AFR exome AF: 0.186

Gnomad4 AMR exome AF: 0.0118

Gnomad4 ASJ exome AF: 0.0117

Gnomad4 EAS exome AF: 0.00232

Gnomad4 SAS exome AF: 0.00432

Gnomad4 FIN exome AF: 0.000131

Gnomad4 NFE exome AF: 0.000624

Gnomad4 OTH exome AF: 0.0143

GnomAD4 genome AF: 0.0537 AC: 8170 AN: 152260 Hom.: 656 Cov.: 33 AF XY: 0.0515 AC XY: 3832 AN XY: 74440

Gnomad4 AFR AF: 0.182

Gnomad4 AMR AF: 0.0207

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.00790

Gnomad4 SAS AF: 0.00622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000926

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0247 Hom.: 145

Bravo AF: 0.0606

Asia WGS AF: 0.0240 AC: 83 AN: 3478

EpiCase AF: 0.00104

EpiControl AF: 0.00172

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Anterior segment dysgenesis 7 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 25, 2024

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 18, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	0.86
Dann	Benign	0.68

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000037
dbscSNV1_RF	Benign	0.062
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: rs73178792; hg19: chr2-1658166; COSMIC: COSV53242667; COSMIC: COSV53242667;