rs112464110
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 6P and 2B. PM1PM2PM5BP4_Moderate
The NM_001142800.2(EYS):c.2500G>T(p.Val834Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000132 in 152,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V834I) has been classified as Likely benign.
Frequency
Consequence
NM_001142800.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
EYS | NM_001142800.2 | c.2500G>T | p.Val834Leu | missense_variant | 16/43 | ENST00000503581.6 | |
EYS | NM_001292009.2 | c.2500G>T | p.Val834Leu | missense_variant | 16/44 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
EYS | ENST00000503581.6 | c.2500G>T | p.Val834Leu | missense_variant | 16/43 | 5 | NM_001142800.2 | A2 | |
EYS | ENST00000370621.7 | c.2500G>T | p.Val834Leu | missense_variant | 16/44 | 1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 32
GnomAD4 exome Cov.: 33
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74276
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 17, 2022 | This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 834 of the EYS protein (p.Val834Leu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with EYS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at