rs374541202
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The ENST00000566780.6(WWOX):āc.898A>Gā(p.Asn300Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000248 in 1,614,246 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N300S) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000566780.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
WWOX | NM_016373.4 | c.898A>G | p.Asn300Asp | missense_variant | 8/9 | ENST00000566780.6 | NP_057457.1 | |
WWOX | NM_001291997.2 | c.559A>G | p.Asn187Asp | missense_variant | 7/8 | NP_001278926.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
WWOX | ENST00000566780.6 | c.898A>G | p.Asn300Asp | missense_variant | 8/9 | 1 | NM_016373.4 | ENSP00000457230 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000118 AC: 18AN: 152238Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 249574Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135402
GnomAD4 exome AF: 0.0000150 AC: 22AN: 1461890Hom.: 0 Cov.: 32 AF XY: 0.0000179 AC XY: 13AN XY: 727248
GnomAD4 genome AF: 0.000118 AC: 18AN: 152356Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74492
ClinVar
Submissions by phenotype
not provided Uncertain:4
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2024 | WWOX: PM2, PP3 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 17, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Mayo Clinic Laboratories, Mayo Clinic | Aug 04, 2022 | PP3, PM2 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 18, 2023 | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25411445) - |
Autosomal recessive spinocerebellar ataxia 12;C3463992:Developmental and epileptic encephalopathy, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Sep 01, 2022 | This sequence change replaces asparagine with aspartic acid at codon 300 of the WWOX protein (p.Asn300Asp). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is present in population databases (rs374541202, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with WWOX-related conditions. ClinVar contains an entry for this variant (Variation ID: 241107). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Not Available"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Not Available"). 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. - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 11, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at