ClinVar Miner

Submissions for variant NM_016628.5(WAC):c.263_266del (p.Glu88fs)

dbSNP: rs864321689
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx 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

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