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Gene-disease assertions not curated here (add link or write note):
Disease FORMAT: HEADING 1 | Vertebral hypersegmentation and orofacial anomalies |
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Inheritance | Autosomal recessive / autosomal dominant / X-linked |
Prevalence | Source: |
Rapid or full curation? | |
ClinGen / GenCC / BabySeq / HGMD/ OMIM | GenCC: vertebral hypersegmentation and orofacial anomalies (Strong- G2P 12/7/2021; Limited- Invitae 12/23/2020) OMIM: AD ?Vertebral hypersegmentation and orofacial anomalies (MIM#619122) HGMD: |
Clinical Validity Scoring Notes and points | Variant/Case Evidence: PMID: 31215115 (Cox 2019)- 1 proband with p.Arg298Gln variant (0.5 pts) PMID: 34113007 (Ravencroft 2021)- 6 probands total; Pt 1: de novo p.Y336* (2.5 pts), Pt 2: inherited p.Q147Gfs*82 (2 pts), Pt 3: de novo p.T319Nfs*5 (2.5 pts), Pt 4: inherited p.N94Rfs*47 (2 pts), Pt 5: de novo p.R295P (1 pt), Pt 6 de novo p.E306K (1 pt)
Segregation Evidence: Case/Control Evidence: Experimental Evidence: Source: |
Clinical Validity Points Total | >12 pts Source: |
Clinical Validity Classification | Expand |
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| title | Classifications (pts) |
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| Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed |
| Source: Definitive (12pts) |
Molecular Mechanism | Expand |
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| Loss of function Gain of function Dominant negative Unknown Other |
| Loss of function / Gain of function / Dominant Negative Several papers suggest: Loss of Function. It is predicted that the missense variants impacting the RXXR motif behave like LOF because TGF-B domain is not cleaved. PMID: 34113007 (Ravencroft 2021) |
Penetrance | Expand |
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| Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) |
(list source/PMID) | Source: |
Age of Onset | Expand |
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| Congenital Pediatric Adolescent Adulthood Late adulthood |
(list source/PMID) | |
Severity | Expand |
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| Embryonic lethal - presence of a pathogenic variant or variants is not compatible with life. The penetrance must be complete.
Severe - presence of a pathogenic variant or variant(s) results in significantly reduced fitness. The penetrance must be complete or high.
Moderate - significant morbidity or mortality due to clinical features, but fitness may not be reduced, or penetrance is reduced.
Mild - Presence of a variant or variant(s) is not associated with reduced fitness, no significant morbidity or mortality, and/or penetrance is low.
None - presence of a variant results in no phenotype. An example is recessive disorders in which no phenotype is reported in carriers. |
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Clinical Features | Sources: |
HPO Terms https://hpo.jax.org/app/ | |
Gene SOPs & Notes | LINK if SOP is a long document. Short notes if it is easy to digest. eg. Last known truncating variant |
Curation Summary | Expand |
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| - The @GENE@ is associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Variable expression or severity:
The severity and expressivity of the disorder is highly variable, even within families.
- If multiple conditions associated with the gene:
It has also been associated with @inheritance pattern@ @condition@, which is characterized by @clinical features@ (PMIDs). - Limited evidence gene: The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dIsease relationship is limited |
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Case ID, Curator name, Date, Jira ticket link | |
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