PCNA Gene Curation

Inheritance

Autosomal recessive

Prevalence

 1/100,000 (rare, based on ataxia-telangiectasia prevalence)

Source: Orphanet

Rapid or full curation?

ClinGen / GenCC / BabySeq / HGMD

No curations in ClinGen, LIMITED BY INVITAE ( 01/10/2020) IN GENCC, not in BabySeq

2 variants in HGMD

Clinical Validity Scoring Notes and points

Variant/Case Evidence:

• c.443G>C p.C148S (1/34520 Latino chr, 0.00003)  - 33426167 - variant in case 2, 11yo girl with slow progressive ataxia since 3yo, mild cognitive dysfunction, hearing loss, non-consanguineous parents, slurred speech, mild oculomotor apraxia, reduced deep tendon reflexes. Subtle and isolated telangiectasias. WES identified the variant. 1POINT

• c.683G>T p.S228I (2/113706 Eur non-Finnish gnomAD, 0.00001). PMID: 24911150 - short stature, hearing loss, premature aging, telangiectasia, neurodegneration, photosensitivity, variant homozygous. Patient cells had excibited marked abnormalities in response to UV radiation. Fig 1, family consanguineous. Linkage and sequencing of all protein coding genes in the region was performed. Fig 1, 3 affected segs, 10 unaffected segs, 2 POINTS

Segregation Evidence: none

Case/Control Evidence: none

Experimental Evidence: none

Source: noted in case evidence above

Clinical Validity Points Total

3

Clinical Validity Classification

Limited

Molecular Mechanism

N/A

Penetrance

(list source/PMID)

N/A

Age of Onset

(list source/PMID)

N/A

Severity

N/A

Clinical Features

N/A

Sources:

Gene SOPs & Notes

Curation Summary:

The PCNA gene has been reported in individuals with early onset autosomal recessive ataxia (PMID: 33426167, 24911150), however, evidence supporting this gene-dsiease relationship is limited

Case ID, Curator name, Date, Jira ticket link

Andrea Oza, 06/14/2024 https://broadinstitute.atlassian.net/browse/CIT-127