Menu
GeneBe

rs115076385

chr2-1648582-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_012293.3(PXDN):c.3198C>T(p.Ala1066=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0114 in 1,613,832 control chromosomes in the GnomAD database, including 162 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0073 ( 3 hom., cov: 33)
Exomes 𝑓: 0.012 ( 159 hom. )

Consequence

PXDN
NM_012293.3 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.837
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.5).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-1648582-G-A is Benign according to our data. Variant chr2-1648582-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 260226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.837 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00733 (1117/152342) while in subpopulation SAS AF= 0.0211 (102/4830). AF 95% confidence interval is 0.0178. There are 3 homozygotes in gnomad4. There are 545 alleles in male gnomad4 subpopulation. This position pass quality control queck.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
PXDNNM_012293.3 linkuse as main transcriptc.3198C>T p.Ala1066= synonymous_variant 17/23 ENST00000252804.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
PXDNENST00000252804.9 linkuse as main transcriptc.3198C>T p.Ala1066= synonymous_variant 17/231 NM_012293.3 P1Q92626-1
PXDNENST00000478155.5 linkuse as main transcriptn.2697-3830C>T intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00733
AC:
1116
AN:
152224
Hom.:
3
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00195
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00674
Gnomad ASJ
AF:
0.0144
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0209
Gnomad FIN
AF:
0.00132
Gnomad MID
AF:
0.00637
Gnomad NFE
AF:
0.0110
Gnomad OTH
AF:
0.00717
GnomAD3 exomes
AF:
0.00910
AC:
2266
AN:
248934
Hom.:
22
AF XY:
0.0101
AC XY:
1361
AN XY:
135022
show subpopulations
Gnomad AFR exome
AF:
0.00186
Gnomad AMR exome
AF:
0.00397
Gnomad ASJ exome
AF:
0.0148
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0227
Gnomad FIN exome
AF:
0.00112
Gnomad NFE exome
AF:
0.0105
Gnomad OTH exome
AF:
0.00776
GnomAD4 exome
AF:
0.0118
AC:
17273
AN:
1461490
Hom.:
159
Cov.:
32
AF XY:
0.0121
AC XY:
8833
AN XY:
727016
show subpopulations
Gnomad4 AFR exome
AF:
0.00149
Gnomad4 AMR exome
AF:
0.00434
Gnomad4 ASJ exome
AF:
0.0168
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0232
Gnomad4 FIN exome
AF:
0.00188
Gnomad4 NFE exome
AF:
0.0124
Gnomad4 OTH exome
AF:
0.0103
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.00733
AC:
1117
AN:
152342
Hom.:
3
Cov.:
33
AF XY:
0.00732
AC XY:
545
AN XY:
74494
show subpopulations
Gnomad4 AFR
AF:
0.00195
Gnomad4 AMR
AF:
0.00673
Gnomad4 ASJ
AF:
0.0144
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0211
Gnomad4 FIN
AF:
0.00132
Gnomad4 NFE
AF:
0.0110
Gnomad4 OTH
AF:
0.00710
Alfa
AF:
0.00972
Hom.:
6
Bravo
AF:
0.00720
Asia WGS
AF:
0.00664
AC:
23
AN:
3478
EpiCase
AF:
0.0110
EpiControl
AF:
0.0122

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Anterior segment dysgenesis 7 Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeJan 18, 2024- -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingGeneDxJun 11, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.50
Cadd
Benign
6.2
Dann
Benign
0.69

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs115076385; hg19: chr2-1652354; API