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Severe microcephaly v9.3 VPS51 Ida Ertmanska Classified gene: VPS51 as Amber List (moderate evidence)
Severe microcephaly v9.3 VPS51 Ida Ertmanska Added comment: Comment on list classification: There are now 4 unrelated patients reported with biallelic VPS51 variants and severe syndromic ID / GDD. While severity was not stated, microcephaly was a consistent feature in all individuals. Hence, this gene can be promoted to Green at the next update.
Severe microcephaly v9.3 VPS51 Ida Ertmanska Gene: vps51 has been classified as Amber List (Moderate Evidence).
Severe microcephaly v9.2 VPS51 Ida Ertmanska gene: VPS51 was added
gene: VPS51 was added to Severe microcephaly. Sources: Literature
Q2_26_promote_green tags were added to gene: VPS51.
Mode of inheritance for gene: VPS51 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: VPS51 were set to 30624672; 31207318; 40176246; 40565173
Phenotypes for gene: VPS51 were set to Pontocerebellar hypoplasia, type 13, OMIM:618606; pontocerebellar hypoplasia, type 13, MONDO:0032831; neurodevelopmental disorder, MONDO:0700092
Review for gene: VPS51 was set to GREEN
Added comment: PMID: 40565173 Aygun et al., 2025
2 sibs exhibiting developmental delay, a thin corpus callosum, severe intellectual disability, epilepsy, microcephaly, hearing loss, and dysphagia. Both homozygous for a c.1511C>T; p.Thr504Met VPS51 variant.

PMID: 40176246 Bhanudeep & Koneti, 2025
Proband: 15 month old boy with severe global developmental delay, failure to thrive, microcephaly, generalized hypotonia, nystagmus, Brisk DTRs. Neuroimaging showed diffuse hypomyelinated white matter, severely hypoplastic corpus callosum, and cerebral and cerebellar atrophy. WES revealed a homozygous VPS51 duplication p.Lys126_Met132dup.

PMID: 30624672 (2019) - 6-year-old girl with severe global developmental delay, pontocerebellar abnormalities, microcephaly, hypotonia, epilepsy and several systemic and peripheral dysfunctions. Exome sequencing revealed compound heterozygous variants in VPS51 ([c.2232delC; p.Asp745Thrfs*93];[c.1468C>T; p.Arg490Cys]). Functional studies of both variants indicate impaired function of the mutant protein.

PMID: 31207318 (2019) - two sisters with a homozygous three bp in-frame deletion (c.1419_1421del; p.Phe474del) in VPS51 associated with developmental delay, absent speech, severe ID and microcephaly. Development in both sisters was initially unremarkable; however, following an episode of fever (at 1 and 12 months of age, respectively), pyschomotor development was severely delayed. At 30 months and 9 years of age, respectively, neither sister had any language. No functional studies of the variant or patient cells were undertaken.
Sources: Literature