ClinVar Miner

Submissions for variant NM_000157.4(GBA):c.115+1G>A (rs104886460)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000177098 SCV000485109 pathogenic Gaucher's disease, type 1 2016-02-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000790724 SCV000228922 pathogenic not provided 2015-09-03 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000762856 SCV000893216 pathogenic Lewy body dementia; Gaucher's disease, type 1; Acute neuronopathic Gaucher's disease; Subacute neuronopathic Gaucher's disease; Gaucher disease, perinatal lethal; Gaucher disease type 3C; Parkinson disease, late-onset 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000032094 SCV000054468 pathologic Gaucher disease 2011-02-01 no assertion criteria provided curation Converted during submission to Pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000032094 SCV000697575 pathogenic Gaucher disease 2016-08-11 criteria provided, single submitter clinical testing Variant summary: The GBA c.115+1G>A variant involves the alteration of a conserved intronic splice-site nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict that this variant eliminates the splicing donor site, which has been confirmed in one patient using cDNA sequencing. This variant has been reported in numerous patients with Gaucher disease. This variant was found in 14/121336 control chromosomes at a frequency of 0.0001154, which does not exceed the estimated maximal expected allele frequency of a pathogenic GBA variant (0.005). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000790724 SCV000935506 pathogenic not provided 2018-10-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 3 of the GBA gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. The frequency data for this variant in the population databases (rs104886460, ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has been observed in individuals affected with Gaucher disease (PMID: 27682613, 23430873) and Parkinson's disease (PMID: 25653295, 20816920, 26117366). This variant is also known as IVS2+1 in the literature. ClinVar contains an entry for this variant (Variation ID: 93445). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and 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 RCV000177098 SCV000024719 pathogenic Gaucher's disease, type 1 2000-01-01 no assertion criteria provided literature only
OMIM RCV000004546 SCV000024720 pathogenic Acute neuronopathic Gaucher's disease 2000-01-01 no assertion criteria provided literature only

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