chr10-100750701-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PM1PP3_ModerateBS2
The NM_000278.5(PAX2):c.220G>A(p.Glu74Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,942 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000278.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251218Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135820
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461758Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727184
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74348
ClinVar
Submissions by phenotype
Renal coloboma syndrome Uncertain:1
This PAX2 variant (rs754146050) is rare (<0.1%) in a large population dataset (gnomAD: 2/282616 total alleles; 0.0007%; no homozygotes). It has been reported in ClinVar (Variation ID 1469446), but has not been reported in the literature, to our knowledge. Three bioinformatic tools queried predict that this substitution would be damaging, and glutamic acid at this position is evolutionarily conserved across all species assessed. We consider the clinical significance of c.220G>A to be uncertain at this time. -
Renal coloboma syndrome;C4014925:Focal segmental glomerulosclerosis 7 Uncertain:1
In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1469446). This variant has not been reported in the literature in individuals affected with PAX2-related conditions. This variant is present in population databases (rs754146050, gnomAD 0.008%). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 74 of the PAX2 protein (p.Glu74Lys). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at