chr2-232747740-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001103146.3(GIGYF2):āc.167A>Gā(p.Asn56Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000384 in 1,613,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Consequence
NM_001103146.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.000309 AC: 47AN: 152234Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000263 AC: 66AN: 251020Hom.: 0 AF XY: 0.000199 AC XY: 27AN XY: 135700
GnomAD4 exome AF: 0.000392 AC: 573AN: 1461302Hom.: 0 Cov.: 31 AF XY: 0.000348 AC XY: 253AN XY: 726984
GnomAD4 genome AF: 0.000308 AC: 47AN: 152352Hom.: 0 Cov.: 32 AF XY: 0.000282 AC XY: 21AN XY: 74506
ClinVar
Submissions by phenotype
not specified Uncertain:1
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. -
GIGYF2-related disorder Uncertain:1
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. -
not provided Uncertain:1
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Parkinson disease 11, autosomal dominant, susceptibility to Other:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at