2-1649211-AG-AGG
Variant summary
Our verdict is Pathogenic. Variant got 10 ACMG points: 10P and 0B. PVS1PM2
The NM_012293.3(PXDN):c.2568_2569insC(p.Cys857LeufsTer10) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,510,576 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000068 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000015 ( 0 hom. )
Consequence
PXDN
NM_012293.3 frameshift
NM_012293.3 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: -0.770
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]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 10 ACMG points.
PVS1
?
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PXDN | NM_012293.3 | c.2568_2569insC | p.Cys857LeufsTer10 | frameshift_variant | 17/23 | ENST00000252804.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PXDN | ENST00000252804.9 | c.2568_2569insC | p.Cys857LeufsTer10 | frameshift_variant | 17/23 | 1 | NM_012293.3 | P1 | |
PXDN | ENST00000478155.5 | n.2696+4416_2696+4417insC | intron_variant, non_coding_transcript_variant | 2 | |||||
PXDN | ENST00000493779.1 | downstream_gene_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000684 AC: 1AN: 146182Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.0000154 AC: 21AN: 1364394Hom.: 0 Cov.: 77 AF XY: 0.0000191 AC XY: 13AN XY: 679524
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ClinVar
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at