rs34424361
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BS1BS2
The NM_001103146.3(GIGYF2):c.3855G>A(p.Ser1285Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0181 in 1,613,144 control chromosomes in the GnomAD database, including 332 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.016 ( 28 hom., cov: 32)
Exomes 𝑓: 0.018 ( 304 hom. )
Consequence
GIGYF2
NM_001103146.3 synonymous
NM_001103146.3 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.840
Genes affected
GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.56).
BP6
Variant 2-232856815-G-A is Benign according to our data. Variant chr2-232856815-G-A is described in ClinVar as [Benign]. Clinvar id is 3038024.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-232856815-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-0.84 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0155 (2365/152182) while in subpopulation NFE AF= 0.0193 (1311/68002). AF 95% confidence interval is 0.0184. There are 28 homozygotes in gnomad4. There are 1288 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
High AC in GnomAd4 at 2365 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GIGYF2 | NM_001103146.3 | c.3855G>A | p.Ser1285Ser | synonymous_variant | 29/29 | ENST00000373563.9 | NP_001096616.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GIGYF2 | ENST00000373563.9 | c.3855G>A | p.Ser1285Ser | synonymous_variant | 29/29 | 1 | NM_001103146.3 | ENSP00000362664.5 |
Frequencies
GnomAD3 genomes AF: 0.0156 AC: 2367AN: 152064Hom.: 28 Cov.: 32
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GnomAD3 exomes AF: 0.0168 AC: 4234AN: 251366Hom.: 62 AF XY: 0.0168 AC XY: 2286AN XY: 135850
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GnomAD4 exome AF: 0.0184 AC: 26888AN: 1460962Hom.: 304 Cov.: 30 AF XY: 0.0181 AC XY: 13126AN XY: 726860
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GnomAD4 genome AF: 0.0155 AC: 2365AN: 152182Hom.: 28 Cov.: 32 AF XY: 0.0173 AC XY: 1288AN XY: 74398
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ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
GIGYF2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 15, 2019 | 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). - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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