2-1635288-A-G

Position:

• chr2-1635288-A-G

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+120T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 819,114 control chromosomes in the GnomAD database, including 32,617 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6092 hom., cov: 33)
  • Exomes 𝑓: 0.27 (26525 hom.)
• Consequence: PXDN NM_012293.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.75

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]

LOC124907723 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 2-1635288-A-G is Benign according to our data. Variant chr2-1635288-A-G is described in ClinVar as [Benign]. Clinvar id is 1256952.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.385 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PXDN	NM_012293.3	c.4320+120T>C		intron_variant		ENST00000252804.9	NP_036425.1
LOC124907723	XR_007086188.1	n.344-397A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PXDN	ENST00000252804.9	c.4320+120T>C		intron_variant		1	NM_012293.3	ENSP00000252804	P1
PXDN	ENST00000453308.1	c.*110+120T>C		intron_variant, NMD_transcript_variant		3		ENSP00000414098
PXDN	ENST00000478155.5	n.3408+120T>C		intron_variant, non_coding_transcript_variant		2
PXDN	ENST00000493654.1	n.1657+120T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41862 AN: 152010 Hom.: 6072 Cov.: 33

Gnomad AFR AF: 0.294

Gnomad AMI AF: 0.225

Gnomad AMR AF: 0.374

Gnomad ASJ AF: 0.326

Gnomad EAS AF: 0.398

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.236

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.229

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.272 AC: 181207 AN: 666986 Hom.: 26525 AF XY: 0.276 AC XY: 97465 AN XY: 353342

Gnomad4 AFR exome AF: 0.290

Gnomad4 AMR exome AF: 0.429

Gnomad4 ASJ exome AF: 0.325

Gnomad4 EAS exome AF: 0.406

Gnomad4 SAS exome AF: 0.382

Gnomad4 FIN exome AF: 0.224

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.270

GnomAD4 genome AF: 0.276 AC: 41925 AN: 152128 Hom.: 6092 Cov.: 33 AF XY: 0.282 AC XY: 21003 AN XY: 74384

Gnomad4 AFR AF: 0.294

Gnomad4 AMR AF: 0.374

Gnomad4 ASJ AF: 0.326

Gnomad4 EAS AF: 0.399

Gnomad4 SAS AF: 0.388

Gnomad4 FIN AF: 0.236

Gnomad4 NFE AF: 0.229

Gnomad4 OTH AF: 0.277

Alfa AF: 0.249 Hom.: 5720

Bravo AF: 0.286

Asia WGS AF: 0.395 AC: 1370 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	Jul 27, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.019
DANN	Benign	0.48

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: rs2241458; hg19: chr2-1639060; COSMIC: COSV53235604;