Familial breast cancer
Gene: ATRIPComment on list classification: New gene added to this panel by Lauma Freimane. More evidence is required prior to adding this gene to the panel. The metanalysis paper identified by reviewer is still at the preprint stage. The findings are detailed below but this needs to be revisited once the article has been published. This is a good candidate gene for breast cancer susceptibility but for now can only classify as Amber (with watchlist tag), awaiting peer-review and additional publication of supporting evidence.Created: 5 Jul 2023, 11:28 a.m. | Last Modified: 5 Jul 2023, 11:28 a.m.
Panel Version: 1.19
Enrichment for ATRIP variants was found in meta-analysis of breast cancer cohorts and UK Biobank. ATRIP carriers had a higher proportion of high-grade, low-stage ductal breast cancer but none of the associations with tumor characteristics were statistically significant (https://doi.org/10.1101/2022.06.17.22276537).
Another study (PMID: 36977412) also identified three Polish women with familial breast cancer and variants in this gene including a c.69_75dup (p.Thr26Alafs∗23) frameshift insertion (not discussed further in paper) and a founder c.1152_1155del (p.Gly385Ter) frameshift deletion in two women. The founder variant was also found in validation cohorts with 42/16,085 unselected Polish breast cancer-affected individuals and 11/9,285 control subjects (OR = 2.14, 95% CI = 1.13-4.28, p = 0.02) harbouring the variant. UK Biobank data showed ATRIP loss-of-function variants among 13/15,643 breast cancer-affected individuals versus 40/157,943 control subjects (OR = 3.28, 95% CI = 1.76-6.14, p < 0.001).
Immunohistochemistry and functional studies showed the ATRIP c.1152_1155del variant allele is weakly expressed compared to the wild-type allele, and truncated ATRIP fails to perform its normal function to prevent replicative stress.
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ATRIP is currently not associated with any phenotype in OMIM or G2P. It codes for a DNA damage response protein which forms a complex with ATR. ATR-ATRIP is involved in the process that activates checkpoint signalling when single-stranded DNA is detected following the processing of DNA double-stranded breaks or stalled replication forks.Created: 5 Jul 2023, 11:27 a.m. | Last Modified: 5 Jul 2023, 11:27 a.m.
Panel Version: 1.18
Meta-analysis confirms ATRIP role in breast cancer development (https://doi.org/10.1101/2022.06.17.22276537).
Variants in ATRIP are associated with breast cancer susceptibility in the Polish population and UK Biobank.
Sources: LiteratureCreated: 17 May 2023, 1:52 p.m.
Mode of inheritance
Unknown
Phenotypes
Hereditary breast cancer
Publications
Variants in this GENE are reported as part of current diagnostic practice
Mode of inheritance for gene: ATRIP was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Gene: atrip has been classified as Amber List (Moderate Evidence).
gene: ATRIP was added gene: ATRIP was added to Familial breast cancer. Sources: Literature Mode of inheritance for gene: ATRIP was set to Unknown Publications for gene: ATRIP were set to 36977412 Phenotypes for gene: ATRIP were set to Hereditary breast cancer Review for gene: ATRIP was set to GREEN gene: ATRIP was marked as current diagnostic