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HERC2 Gene Curation

HERC2 Gene Curation

Owned by Andrea Oza
2025-02-04
2 min read

Gene-disease assertions not curated here (add link or write note):

Disease

developmental delay with autism spectrum disorder and gait instability

Disease

developmental delay with autism spectrum disorder and gait instability

Inheritance

Autosomal recessive

Prevalence

Orphanet

Medline Plus Genetics

 <1 / 1 000 000

Source: ORPHANET

Rapid or full curation?

Rapid - curating for mol mech only
Full

ClinGen / GenCC / BabySeq / HGMD / OMIM

ClinGen - none; GenCC Strong (Invitae), Moderate (Ambry).

Clinical Validity Scoring Notes and points

Not necessary, strong/moderate curations in GenCC.

Source:

Clinical Validity Points Total

 

Source:

Clinical Validity Classification

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

 

Source:

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

Loss of function

 

PMID: 34370298

  • Patient 8 HOM c.9710T>A p.L3237* (absent gAD v4)

  • Patient 2 HOM c.9490C>T Q3164X (1 allele gAD v4). - citing Yavarna et al 2015 PMID: 26077850

    Patient 3 HOM c.13767_13770delTGAA p.Asn4589Lysfs*9 (absent gAD v4)- citing Elpidorou 2020 PMID 32571899

    Patient 6 cmp het with c.5976_5977insAT p.Leu1993Ilefs*9 (absent gAD v4), c.1483_1484delAT p.Ile495Cysfs*8 (absent gAD v4)

 

Sources: 34370298, 26077850, 32571899

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

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.

 

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

- 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

 

Case ID, Curator name, Date, Jira ticket link

AO, E3850510438, 02/04/25

 

 

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