ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1830+1G>C (rs80338677)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000020364 SCV000220221 pathogenic Deficiency of alpha-mannosidase 2014-04-03 criteria provided, single submitter literature only
Ambry Genetics RCV000622767 SCV000742222 pathogenic Inborn genetic diseases 2017-05-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: POSITIVE: Relevant Alteration(s) Detected
Integrated Genetics/Laboratory Corporation of America RCV000020364 SCV001364017 pathogenic Deficiency of alpha-mannosidase 2019-11-25 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.1830+1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 9.3e-05 in 248630 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MAN2B1 causing Alpha-Mannosidosis (9.3e-05 vs 0.0016). c.1830+1G>C has been reported in the literature as one of the most common disease causing variants in multiple individuals affected with Alpha-Mannosidosis (example, Riise Stensland_2012, Berg_1999). These data indicate that the variant is very likely to be associated with disease. No experimental evidence demonstrating an impact on protein function were ascertained within the context of this evaluation. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneReviews RCV000020364 SCV000040751 pathologic Deficiency of alpha-mannosidase 2012-05-03 no assertion criteria provided curation Converted during submission to Pathogenic.
OMIM RCV000020364 SCV000056374 pathogenic Deficiency of alpha-mannosidase 2012-03-01 no assertion criteria provided literature only

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