chr2-1648687-G-A

Variant names:

• chr2-1648687-G-A
• rs6752525
• NM_012293.3:c.3093C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_012293.3(PXDN):​c.3093C>T​(p.Tyr1031Tyr) variant causes a synonymous change. The variant allele was found at a frequency of 0.00689 in 1,607,828 control chromosomes in the GnomAD database, including 581 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.035 (295 hom., cov: 32)
  • Exomes 𝑓: 0.0039 (286 hom.)
• Consequence: PXDN NM_012293.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 4.08
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• anterior segment dysgenesis 7

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 2-1648687-G-A is Benign according to our data. Variant chr2-1648687-G-A is described in ClinVar as Benign. ClinVar VariationId is 260225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012293.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	NM_012293.3	MANE Select	c.3093C>T	p.Tyr1031Tyr	synonymous	Exon 17 of 23	NP_036425.1	Q92626-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PXDN	ENST00000252804.9	TSL:1 MANE Select	c.3093C>T	p.Tyr1031Tyr	synonymous	Exon 17 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000857505.1		c.3021C>T	p.Tyr1007Tyr	synonymous	Exon 16 of 22	ENSP00000527564.1
	PXDN	ENST00000478155.5	TSL:2	n.2697-3935C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 5349 AN: 152114 Hom.: 295 Cov.: 32

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00814

Gnomad SAS AF: 0.00580

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000412

Gnomad OTH AF: 0.0335

GnomAD2 exomes AF: 0.00974 AC: 2311 AN: 237238 AF XY: 0.00771

Gnomad AFR exome AF: 0.127

Gnomad AMR exome AF: 0.00604

Gnomad ASJ exome AF: 0.000204

Gnomad EAS exome AF: 0.00602

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000270

Gnomad OTH exome AF: 0.00597

GnomAD4 exome AF: 0.00393 AC: 5717 AN: 1455596 Hom.: 286 Cov.: 32 AF XY: 0.00349 AC XY: 2528 AN XY: 723424

African (AFR) AF: 0.125 AC: 4180 AN: 33330

American (AMR) AF: 0.00694 AC: 305 AN: 43976

Ashkenazi Jewish (ASJ) AF: 0.0000385 AC: 1 AN: 25994

East Asian (EAS) AF: 0.00231 AC: 91 AN: 39410

South Asian (SAS) AF: 0.00410 AC: 348 AN: 84914

European-Finnish (FIN) AF: 0.0000190 AC: 1 AN: 52500

Middle Eastern (MID) AF: 0.00694 AC: 40 AN: 5764

European-Non Finnish (NFE) AF: 0.000199 AC: 221 AN: 1109548

Other (OTH) AF: 0.00881 AC: 530 AN: 60160

GnomAD4 genome AF: 0.0352 AC: 5364 AN: 152232 Hom.: 295 Cov.: 32 AF XY: 0.0342 AC XY: 2544 AN XY: 74432

African (AFR) AF: 0.120 AC: 4980 AN: 41514

American (AMR) AF: 0.0138 AC: 212 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00816 AC: 42 AN: 5150

South Asian (SAS) AF: 0.00580 AC: 28 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000412 AC: 28 AN: 68030

Other (OTH) AF: 0.0336 AC: 71 AN: 2114

Alfa AF: 0.0161 Hom.: 68

Bravo AF: 0.0400

Asia WGS AF: 0.0170 AC: 60 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Anterior segment dysgenesis 7 (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	4.4
DANN	Benign	0.56
PhyloP100		4.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6752525; hg19: chr2-1652459;