ClinVar Miner

Submissions for variant NM_000157.4(GBA):c.1265_1319del (p.Leu422fs) (rs80356768)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000723462 SCV000224865 pathogenic not provided 2014-05-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000020147 SCV000697578 pathogenic Gaucher disease 2016-05-19 criteria provided, single submitter clinical testing Variant summary: The c.1265_1319del55 variant in GBA involves the deletion of 55 nucleotides, resulting in a premature termination codon, predicted to cause a truncated or absent GBA protein due to nonsense mediated decay. This deletion in exon 10 (exon 9 legacy) is thought to be the result of recombination between GBA and GBAP (a GBA pseudogene). The frequency of the variant in the large and diverse ExAC database cannot be determined as the sequencing technology used typically cannot detect deletions this large. However, the variant has been tested in at least 788 controls in the literature and was not found. The variant was reported in the literature in numerous affected individuals, and has been classified by multiple reputable clinical labs/databases as pathogenic. Taken together, this variant has been classified as pathogenic.
Invitae RCV000723462 SCV000960919 pathogenic not provided 2020-09-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu422Profs*4) in the GBA gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases (rs80356768, ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has been reported in several individuals affected with Gaucher disease (PMID: 17395504, 28727984) and Parkinson's disease (PMID: 20947659). ClinVar contains an entry for this variant (Variation ID: 193611). This variant is also known as c.1263_1317del in the literature. Loss-of-function variants in GBA are known to be pathogenic (PMID: 9153297, 10079102, 10796875, 11783951). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000173718 SCV000024728 pathogenic Gaucher disease type I 2000-03-01 no assertion criteria provided literature only
OMIM RCV000004555 SCV000024729 pathogenic Gaucher disease, perinatal lethal 2000-03-01 no assertion criteria provided literature only
GeneReviews RCV000020147 SCV000040474 pathologic Gaucher disease 2011-02-01 no assertion criteria provided curation Converted during submission to Pathogenic.

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