rs897453553
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBP6
The ENST00000566780.6(WWOX):āc.851A>Gā(p.Lys284Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,614,042 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
ENST00000566780.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.851A>G | p.Lys284Arg | missense_variant | 8/9 | ENST00000566780.6 | NP_057457.1 | |
WWOX | NM_001291997.2 | c.512A>G | p.Lys171Arg | missense_variant | 7/8 | NP_001278926.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WWOX | ENST00000566780.6 | c.851A>G | p.Lys284Arg | missense_variant | 8/9 | 1 | NM_016373.4 | ENSP00000457230 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000920 AC: 14AN: 152188Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000200 AC: 5AN: 249538Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135394
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461854Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727234
GnomAD4 genome AF: 0.0000920 AC: 14AN: 152188Hom.: 0 Cov.: 32 AF XY: 0.000135 AC XY: 10AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, flagged submission | clinical testing | GeneDx | Nov 21, 2016 | A variant of uncertain significance has been identified in the WWOX gene. The K284R variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The K284R variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved and in silico analysis predicts this variant likely does not alter the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 16, 2019 | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 07, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at