ClinVar Miner

Submissions for variant NM_000528.4(MAN2B1):c.1068C>G (p.Pro356=) (rs117880912)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000402847 SCV000410800 likely benign Deficiency of alpha-mannosidase 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Integrated Genetics/Laboratory Corporation of America RCV000780389 SCV000917599 benign not specified 2018-06-15 criteria provided, single submitter clinical testing Variant summary: MAN2B1 c.1068C>G alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0035 in 277160 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 2-fold higher than the estimated maximal expected allele frequency for a pathogenic variant in MAN2B1 causing Alpha-Mannosidosis phenotype (0.0016), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1068C>G in individuals affected with Alpha-Mannosidosis and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) and another clinical diagnostic laboratory (EGL) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000402847 SCV001102341 benign Deficiency of alpha-mannosidase 2019-12-31 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000675483 SCV000801173 likely benign not provided 2015-12-16 no assertion criteria provided clinical testing

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