rs78738655
Variant names:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_000278.5(PAX2):c.932C>T(p.Ala311Val) variant causes a missense change. The variant allele was found at a frequency of 0.000222 in 1,607,932 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.0011 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00013 ( 1 hom. )
Consequence
PAX2
NM_000278.5 missense
NM_000278.5 missense
Scores
2
4
13
Clinical Significance
Conservation
PhyloP100: 6.00
Genes affected
PAX2 (HGNC:8616): (paired box 2) PAX2 encodes paired box gene 2, one of many human homologues of the Drosophila melanogaster gene prd. The central feature of this transcription factor gene family is the conserved DNA-binding paired box domain. PAX2 is believed to be a target of transcriptional supression by the tumor suppressor gene WT1. Mutations within PAX2 have been shown to result in optic nerve colobomas and renal hypoplasia. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Dec 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.011975735).
BP6
Variant 10-100824660-C-T is Benign according to our data. Variant chr10-100824660-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 156301.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=1, not_provided=1}.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00115 (175/152204) while in subpopulation AFR AF= 0.00412 (171/41518). AF 95% confidence interval is 0.00361. There are 0 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 175 AD gene.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.00115 AC: 175AN: 152086Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000414 AC: 104AN: 251442Hom.: 0 AF XY: 0.000287 AC XY: 39AN XY: 135902
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GnomAD4 exome AF: 0.000125 AC: 182AN: 1455728Hom.: 1 Cov.: 31 AF XY: 0.000104 AC XY: 75AN XY: 724486
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GnomAD4 genome AF: 0.00115 AC: 175AN: 152204Hom.: 0 Cov.: 31 AF XY: 0.00120 AC XY: 89AN XY: 74430
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Pathogenic:1Uncertain:1Benign:2Other:1
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
not provided Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Oct 04, 2018 | Has been reported previously in an individual with retinal dystrophy (Carss et al., 2017); Has also been reported previously in an unaffected parent of a child anophthalmia but was not observed in the affected child (Gelb et al., 2001; Bower et al., 2012); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; In addition, in silico splice predictors suggest this variant may lead to abnormal gene splicing; This variant is associated with the following publications: (PMID: 11180607, 22213154, 28041643) - |
not provided, no classification provided | literature only | ClinVar Staff, National Center for Biotechnology Information (NCBI) | - | - - |
Retinal dystrophy Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | NIHR Bioresource Rare Diseases, University of Cambridge | Jan 01, 2015 | - - |
PAX2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 15, 2021 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Renal coloboma syndrome;C4014925:Focal segmental glomerulosclerosis 7 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 28, 2025 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;.
PrimateAI
Pathogenic
T
PROVEAN
Benign
N;.;N;.
REVEL
Benign
Sift
Benign
T;.;T;.
Sift4G
Benign
T;T;T;T
Polyphen
P;D;B;.
Vest4
MVP
MPC
0.31
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at