ClinVar Miner

Submissions for variant NM_025233.7(COASY):c.1549_1550del (p.Ser517fs)

dbSNP: rs766482965
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001585687 SCV001812465 likely pathogenic not provided 2021-06-24 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation as the last 48 amino acids are replaced with 60 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 30089828)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003235379 SCV003934032 pathogenic Neurodegeneration with brain iron accumulation 2023-05-19 criteria provided, single submitter clinical testing Variant summary: COASY c.1549_1550delAG (p.Ser517ProfsX61) causes a frameshift which results in an extension of the protein. The variant allele was found at a frequency of 1.2e-05 in 251012 control chromosomes (gnomAD). c.1549_1550delAG has been reported in the literature in at least one compound heterozygous individual affected with Pontocerebellar hypoplasia, microcephaly and arthrogryposis (van Dijk_2018). These data do not allow any conclusion about variant significance. Amniocytes from this compound heterozygous individual had undetectable levels of COASY protein and ~1% COASY activity compared to controls, indicating loss-of-function (van Dijk_2018). The following publication has been ascertained in the context of this evaluation (PMID: 30089828). Two ClinVar submitters have assessed the variant since 2014: one classified the variant as likely pathogenic, and one as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000735980 SCV000864179 pathogenic Pontocerebellar hypoplasia, type 12 2019-01-09 no assertion criteria provided literature only

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