ABRAXAS1 (aka FAM175A) Gene Curation

Inheritance

N/A

Prevalence

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

Rapid or full curation?

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

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

Gene SOPs & Notes

N/A

Curation Summary:

Not done

Case ID, Curator name, Date, Jira ticket link

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