ClinVar Miner

Submissions for variant NM_001103146.3(GIGYF2):c.167A>G (p.Asn56Ser)

gnomAD frequency: 0.00033  dbSNP: rs72554080
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003398405 SCV004121730 uncertain significance not specified 2023-10-17 criteria provided, single submitter clinical testing Variant summary: GIGYF2 c.167A>G (p.Asn56Ser) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00026 in 251020 control chromosomes. This frequency does not allow conclusions about variant significance. c.167A>G has been reported in the literature with conflicting reports of its association with Parkinson Disease with some studies reporting non-segregation with disease (example Nichols_2009, Vilarino-Guell_2009, Zimprich_2009), questioning the association with Parkinson Disease (example, Vilarino-Guell_2009) and some reporting it as a possible risk factor in Caucasians but not in Asians (example, Zhang_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Parkinson Disease 11, Autosomal Dominant, Susceptibility To. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 19279319, 19133664, 26152800, 19250854). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Mayo Clinic Laboratories, Mayo Clinic RCV004791190 SCV005409086 uncertain significance not provided 2024-07-03 criteria provided, single submitter clinical testing
OMIM RCV000000789 SCV000020939 risk factor Parkinson disease 11, autosomal dominant, susceptibility to 2009-08-01 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004755694 SCV005350541 uncertain significance GIGYF2-related disorder 2024-04-29 no assertion criteria provided clinical testing The GIGYF2 c.167A>G variant is predicted to result in the amino acid substitution p.Asn56Ser. This variant has been reported in individuals with Parkinson disease, although it did not segregate with disease in some families (Lautier et al. 2008. PubMed ID: 18358451; Zimprich et al. 2009. PubMed ID: 19250854; Nichols et al. 2009. PubMed ID: 19279319). It has also been observed in controls (Guella et al. 2010. PubMed ID: 20060621; Meeus et al. 2011. PubMed ID: 19321232). This variant has been described as a risk factor with an odds ratio of 1.7 (95% CI 0.98-2.90, P-value=0.06) reported in a recent publication (Zhang et al. 2015. PubMed ID: 26152800; Supplementary Table 3, Pitz et al. 2024. PubMed ID: 38191580). This variant is reported in 0.050% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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