ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.159+2T>C

dbSNP: rs1057516501
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409222 SCV000485783 likely pathogenic Deficiency of alpha-mannosidase 2016-02-12 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000409222 SCV000915814 uncertain significance Deficiency of alpha-mannosidase 2017-08-21 criteria provided, single submitter clinical testing The MAN2B1 c.159+2T>C variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for alpha-mannosidosis. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Genome-Nilou Lab RCV000409222 SCV001810487 likely pathogenic Deficiency of alpha-mannosidase 2021-07-22 criteria provided, single submitter clinical testing
Invitae RCV000409222 SCV004402084 likely pathogenic Deficiency of alpha-mannosidase 2022-12-31 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 370454). This variant has not been reported in the literature in individuals affected with MAN2B1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 1 of the MAN2B1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MAN2B1 are known to be pathogenic (PMID: 9915946, 22161967).

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