2-1674962-G-A

Position:

• chr2-1674962-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000252804.9(PXDN):​c.849-1150C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 152,082 control chromosomes in the GnomAD database, including 3,952 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (3952 hom., cov: 32)
• Consequence: PXDN ENST00000252804.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3	c.849-1150C>T		intron_variant		ENST00000252804.9	NP_036425.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.849-1150C>T		intron_variant		1	NM_012293.3	ENSP00000252804	P1

Frequencies

GnomAD3 genomes AF: 0.205 AC: 31119 AN: 151964 Hom.: 3941 Cov.: 32

Gnomad AFR AF: 0.0737

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.347

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.308

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.272

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.205 AC: 31143 AN: 152082 Hom.: 3952 Cov.: 32 AF XY: 0.214 AC XY: 15915 AN XY: 74306

Gnomad4 AFR AF: 0.0735

Gnomad4 AMR AF: 0.348

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.309

Gnomad4 SAS AF: 0.350

Gnomad4 FIN AF: 0.272

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.191

Alfa AF: 0.228 Hom.: 2032

Bravo AF: 0.201

Asia WGS AF: 0.275 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.39
DANN	Benign	0.60

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: rs7560004; hg19: chr2-1678734;