2-1643470-C-G

Variant names:

• chr2-1643470-C-G
• NM_012293.3:c.3850G>C
• PXDN p.Val1284Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_012293.3(PXDN):​c.3850G>C​(p.Val1284Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: PXDN NM_012293.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.73
• Publications: 0 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: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3757562).

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.3850G>C	p.Val1284Leu	missense	Exon 19 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.3850G>C	p.Val1284Leu	missense	Exon 19 of 23	ENSP00000252804.4	Q92626-1
	PXDN	ENST00000857505.1		c.3778G>C	p.Val1260Leu	missense	Exon 18 of 22	ENSP00000527564.1
	PXDN	ENST00000453308.1	TSL:3	n.1G>C		non_coding_transcript_exon	Exon 1 of 4	ENSP00000414098.1	H7C3W2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.26	T
Eigen	Benign	0.068
Eigen_PC	Benign	0.18
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.025	T
MetaRNN	Benign	0.38	T
MetaSVM	Benign	-0.61	T
MutationAssessor	Benign	1.7	L
PhyloP100		4.7
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.26
Sift	Benign	0.055	T
Sift4G	Benign	0.078	T
Varity_R		0.22
gMVP		0.72
Mutation Taster		=97/3	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-1647242;