Submissions for variant NM_000528.4(MAN2B1):c.2920dup (p.Thr974fs)

gnomAD frequency: 0.00001  dbSNP: rs774791244

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001872910	SCV002144099	pathogenic	Deficiency of alpha-mannosidase	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the MAN2B1 gene (p.Thr974Asnfs*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 38 amino acid(s) of the MAN2B1 protein and extend the protein by an uncertain number of additional amino acid residues. This variant is present in population databases (rs774791244, gnomAD 0.006%). This frameshift has been observed in individual(s) with alpha-mannosidosis (PMID: 22161967). For these reasons, this variant has been classified as Pathogenic. This variant results in an extension of the MAN2B1 protein. Other variant(s) that result in a similarly extended protein product (p.Thr974Argfs*?) have been determined to be pathogenic (PMID: 22161967). This suggests that these extensions are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1372339).
Fulgent Genetics, Fulgent Genetics	RCV001872910	SCV002807585	likely pathogenic	Deficiency of alpha-mannosidase	2022-04-13	criteria provided, single submitter	clinical testing