rs17841813

Variant names:

• chr2-1660882-A-G
• rs17841813
• NM_012293.3:c.1836T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-1660882-A-G
• chr2-1660882-A-C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4 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
• Publications: 21 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (REVEL=0.26).
• BP6: Variant 2-1660882-A-G is Benign according to our data. Variant chr2-1660882-A-G is described in ClinVar as Benign. ClinVar VariationId 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.

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.1836T>C	p.Asn612Asn	splice_region synonymous	Exon 14 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.1836T>C	p.Asn612Asn	splice_region synonymous	Exon 14 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000433670.5	TSL:1	c.1821T>C	p.Asn607Asn	splice_region synonymous	Exon 14 of 16	ENSP00000402738.1	H7C1W1
	PXDN	ENST00000857505.1		c.1764T>C	p.Asn588Asn	splice_region synonymous	Exon 13 of 22	ENSP00000527564.1

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

GnomAD2 exomes AF: 0.756 AC: 187436 AN: 247928 AF XY: 0.755

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 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

African (AFR) AF: 0.732 AC: 24431 AN: 33382

American (AMR) AF: 0.828 AC: 36930 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.695 AC: 18127 AN: 26064

East Asian (EAS) AF: 0.981 AC: 38843 AN: 39584

South Asian (SAS) AF: 0.855 AC: 73536 AN: 86018

European-Finnish (FIN) AF: 0.680 AC: 36273 AN: 53312

Middle Eastern (MID) AF: 0.742 AC: 3795 AN: 5118

European-Non Finnish (NFE) AF: 0.698 AC: 773031 AN: 1108022

Other (OTH) AF: 0.730 AC: 43856 AN: 60104

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

African (AFR) AF: 0.729 AC: 30227 AN: 41486

American (AMR) AF: 0.754 AC: 11516 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.683 AC: 2372 AN: 3472

East Asian (EAS) AF: 0.977 AC: 5032 AN: 5148

South Asian (SAS) AF: 0.858 AC: 4136 AN: 4820

European-Finnish (FIN) AF: 0.676 AC: 7154 AN: 10584

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.694 AC: 47158 AN: 67980

Other (OTH) AF: 0.714 AC: 1510 AN: 2116

Alfa AF: 0.706 Hom.: 105539

Bravo AF: 0.729

Asia WGS AF: 0.889 AC: 3093 AN: 3478

EpiCase AF: 0.687

EpiControl AF: 0.683

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.081
DANN	Benign	0.62
PhyloP100		-0.19
Mutation Taster		=76/24	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17841813; hg19: chr2-1664654;