6-161785805-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004562.3(PRKN):c.838G>A(p.Asp280Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,910 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 Uncertain significance (★★).
Frequency
Consequence
NM_004562.3 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: 0.0000920 AC: 14AN: 152156Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000163 AC: 41AN: 251122Hom.: 1 AF XY: 0.000184 AC XY: 25AN XY: 135724
GnomAD4 exome AF: 0.000163 AC: 238AN: 1461754Hom.: 1 Cov.: 32 AF XY: 0.000205 AC XY: 149AN XY: 727172
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152156Hom.: 0 Cov.: 33 AF XY: 0.000148 AC XY: 11AN XY: 74318
ClinVar
Submissions by phenotype
Autosomal recessive juvenile Parkinson disease 2 Uncertain:2
The PARK2 c.838G>A (p.Asp280Asn) missense variant gene has been reported in one study and in a compound heterozygous state with a missense variant in one individual affected with early onset Parkinson disease (PD) (Wang et al. 2008). The p.Asp280Asn variant has also been reported in a heterozygous state in several individuals affected with PD (Oliveira et al. 2003; Clark et al. 2006; Bardien et al. 2009; Grunewald et al. 2013). The p.Asp280Asn variant was absent from 500 healthy controls and is reported at a frequency of 0.001047 in the South Asian population of the Genome Aggregation Database, which includes one homozygote (Oliveira et al., 2003; Bardien et al., 2009). Based on the limited evidence, the p.Asp280Asn variant is classified as a variant of unknown significance but suspicious for pathogenicity for juvenile Parkinson disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. -
The missense variant c.838G>A p.Asp280Asn in the PRKN gene has been reported previously in individuals affected with Parkinson's Disease Bardien et al., 2009; Wang et al., 2008. The variant is absent in gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance.The amino acid Aspartic acid at position 280 is changed to a Asparagine changing protein sequence and it might alter its composition and physico-chemical properties. Computational evidence Polyphen - Damaging, SIFT - Tolerated and MutationTaster - Polymorphism predicts conflicting evidence on protein structure and function for this variant. The reference residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at