NAF1 Gene Curation
- Katherine Lafferty
Gene-disease assertions not curated here (add link or write note):
Disease | Telomere-related pulmonary fibrosis and/or bone marrow failure syndrome |
|---|---|
Inheritance | Autosomal dominant |
Prevalence |
Source: |
Rapid or full curation? | Rapid Full |
GenCC- AD Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7 (Invitae- Limited 7/13/2023) OMIM- AD Pulmonary fibrosis and/or bone marrow failure syndrome, telomere-related, 7 | |
Clinical Validity Scoring Notes and points | Variant/Case Evidence: PMID 36028256- 5 variants reported in individuals with idiopathic pulmonary fibrosis (IPF) or familial pulmonary fibrosis (FPF): c.1132dupA p.Thr378fs (0.5pt), c.1123C>T p.Arg375* (0.5pt), c.701G>C p.Arg234Pro (0.1 pt), c.634+1G>T (1pt), c.423_425de lGTC p.Ser142del (0.1 pt). Paper also assessed telomere length but “Individuals carrying [NAF1 variants] did not have significantly shorter WGS-TL although these analyses were limited by small numbers”. (2.2 points) PMID: 27510903- Two pLOF variants reported in individuals with pulmonary fibrosis/short telomere disease. Individuals with these variants had shorter telomere lengths when compared to family members with out the variants (scored as more specific phenotype with telomere length information): c.984insA p.S329Ifs*12 (2 pt), c.956_957delAA p.K319Rfs*21 (2pt). Segregated in one family in 4 affected individuals (4 points) Segregation Evidence: Case/Control Evidence: Experimental Evidence: PMID: 27510903- Cells with truncating mutations showed poor nuclear localization. This function could be rescued by adding an exogenous nuclear localization signal (NLS) (1pt); Mouse model showed NAF1 haploinsufficient mice showed about half the levels of telomerase RNA component (TR). (2 pts). (3 points) Source: |
Clinical Validity Points Total | At least 9.2- Stopped once at Moderate Source: |
Clinical Validity Classification Definitive (12pts) Strong (12pts) Moderate (7-11pts) Limited (0.1-6pts) No genetic evidence Refuted Disputed | Moderate Source: |
Molecular Mechanism Loss of function Gain of function Dominant negative Unknown Other | Loss of function / Gain of function / Dominant Negative
|
Penetrance Complete (100%) High (≥80%) Moderate (<80% and >20%) Low (≤20%) (list source/PMID) |
Source: |
Age of Onset Congenital Pediatric Adolescent Adulthood Late adulthood (list source/PMID) |
|
Severity |
|
Clinical Features |
Sources: |
HPO Terms |
|
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 |
|
Case ID, Curator name, Date, Jira ticket link |
|