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ABRAXAS1 (aka FAM175A) Gene Curation

ABRAXAS1 (aka FAM175A) Gene Curation

Owned by Andrea Oza
2023-06-22
2 min read

Gene-disease assertions not curated here (add link or write note): HGMD - 16 variants present, all cancer syndrome associations

Disease

Cancer predisposition

Disease

Cancer predisposition

Inheritance

N/A

Prevalence

Orphanet

Medline Plus Genetics

Common (different cancers reported, did not select one prevalence, see scoring notes below

Rapid or full curation?

Rapid
Full

ClinGen / GenCC / BabySeq / HGMD

ClinGen - no GCEP curation, no evidence for haploinsufficiency/triplosensitivity

GenCC - no curations

OMIM - no conditions

HGMD - 16 variants present, all cancer syndrome associations, reviewed the truncating variants

Clinical Validity Scoring Notes and points

Reviewed the truncating variants in HGMD, no convincing evidence of cancer predisposition syndrome. Case reports only.

c.10G>T p.E4* - 3 alleles gnomAD. PMID: 2022 in sup data 1, germline variant in patient P0003 with lung cancer (AKA FAM175A).

c.364C>T p.Q122* - PMID: 31263571 - Reported in head and neck cancer in sup table 4

c.774_778delAGGAG p.(Arg258Serfs*33) - PMID: 28975465, in table S4, identified in patient with breast cancer.

c.1027delA p.(Ile343Serfs*7) - PMID: 27433846 - in table S1, in individual from prostate cancer cohort. Germline variant.

c.1106dupG p.Ser370Ilefs*2, in last exon, NMD-. gnomAD 0.05% 13/25109 Finnish. PMID: 26556299 Table S7. Found as germline variant in a diffuse glioma. PMID: 31159747 TABLE S3, found once in this cohort of patients with cancer, most with personal hx of Br or ovarian cancer. No specific details. PMID: 31980526, per HGMD Hereditary cancer-predisposing syndrome; Dataset 1, tab1, classified:VUS [B:4:83462592:T:TC:hg38]

 

 

Clinical Validity Points Total

Clinical Validity Classification

Definitive (12pts)

Strong (12pts)

Moderate (7-11pts)

Limited (0.1-6pts)

No genetic evidence

Refuted

Disputed

Limited

Molecular Mechanism

Loss of function

Gain of function

Dominant negative

Unknown

Other

N/A

Penetrance

Complete (100%)

High (≥90%)

Reduced  (<90% and >10%)

Low (≤10%)

(list source/PMID)

N/A

Age of Onset

Congenital

Pediatric

Adolescent

Adulthood

Late adulthood

(list source/PMID)

N/A

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.

N/A

Clinical Features

N/A

Gene SOPs & Notes

N/A

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-dsiease relationship is limited

Not done

Case ID, Curator name, Date, Jira ticket link

Andrea Oza 06.22.2023 https://broadinstitute.atlassian.net/browse/CIT-127

 

 

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