ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1645-1G>A

gnomAD frequency: 0.00001  dbSNP: rs938576591
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000677673 SCV000803814 likely pathogenic Deficiency of alpha-mannosidase 2015-07-29 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000677673 SCV001591763 pathogenic Deficiency of alpha-mannosidase 2024-03-30 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 13 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). This variant is present in population databases (no rsID available, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967, 31241255). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 559883). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000677673 SCV002014320 pathogenic Deficiency of alpha-mannosidase 2021-09-05 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000677673 SCV002060031 likely pathogenic Deficiency of alpha-mannosidase 2021-11-18 criteria provided, single submitter clinical testing NM_000528.3(MAN2B1):c.1645-1G>A is a canonical splice variant classified as likely pathogenic in the context of alpha-mannosidosis. c.1645-1G>A has been observed in cases with relevant disease (PMID: 22161967, 31241255). Functional assessments of this variant are not available in the literature. c.1645-1G>A has been observed in population frequency databases (gnomAD: NFE < 0.002%). In summary, NM_000528.3(MAN2B1):c.1645-1G>A is a canonical splice variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.
Baylor Genetics RCV000677673 SCV004191897 pathogenic Deficiency of alpha-mannosidase 2023-11-06 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000677673 SCV005655499 pathogenic Deficiency of alpha-mannosidase 2024-04-03 criteria provided, single submitter clinical testing

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