Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000493235 | SCV000582584 | pathogenic | not provided | 2022-10-13 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33004838, 30564305, 25356899) |
Ambry Genetics | RCV001266462 | SCV001444637 | pathogenic | Inborn genetic diseases | 2023-05-19 | criteria provided, single submitter | clinical testing | The c.263_266delAGAG (p.E88Gfs*103) alteration, located in coding exon 3 of the WAC gene, results from a deletion of 4 nucleotides from position 263 to 266, causing a translational frameshift with a predicted alternate stop codon after 103 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This alteration was reported de novo in a 30 year old female with moderate intellectual disability, short 5th metacarpals, and minor dysmorphic features (Hamdan, 2014). Based on the available evidence, this alteration is classified as pathogenic. |
Invitae | RCV000493235 | SCV004295651 | pathogenic | not provided | 2023-08-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 219139). This premature translational stop signal has been observed in individual(s) with WAC-related conditions (PMID: 25356899). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu88Glyfs*103) in the WAC gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in WAC are known to be pathogenic (PMID: 26264232, 26757981). |
OMIM | RCV000203516 | SCV000258621 | pathogenic | DeSanto-Shinawi syndrome due to WAC point mutation | 2014-10-01 | no assertion criteria provided | literature only |