Activity

Filter

Cancel
Date Panel Item Activity
46 actions
Breast cancer pertinent cancer susceptibility v2.8 PTEN Dmitrijs Rots reviewed gene: PTEN: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: PHTS; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Breast cancer pertinent cancer susceptibility v2.8 ATRIP Arina Puzriakova Publications for gene: ATRIP were set to 36977412
Breast cancer pertinent cancer susceptibility v2.7 ATRIP Arina Puzriakova changed review comment from: As reviewed by Dmitrijs Rots (Children's Clinical University Hospital), the previously mentioned metanalysis paper has now been published (PMID: 37592023). This showed that for cases in the Breast Cancer Association Consortium (BCAC) dataset there were 13 carriers of ATRIP protein-truncating variants variants and 9 carriers in UK Biobank (UKB); in controls there were 3 carriers in BCAC and 57 in UKB (p = 0.000106).

I am uncertain whether this is sufficient evidence to add the ATRIP gene as Green to the panel and therefore this will be flagged for further GMS expert review.; to: As reviewed by Dmitrijs Rots (Children's Clinical University Hospital), the previously mentioned metanalysis paper has now been published (PMID: 37592023). This showed that for cases in the Breast Cancer Association Consortium (BCAC) dataset there were 13 carriers of ATRIP protein-truncating variants variants and 9 carriers in UK Biobank (UKB); in controls there were 3 carriers in BCAC and 57 in UKB (p = 0.000106).

This association is also now listed in Gene2Phenotype with a 'moderate' disease confidence category for breast cancer susceptibility.

I am uncertain whether this is sufficient evidence to add the ATRIP gene as Green to the panel and therefore this will be flagged for further GMS expert review.
Breast cancer pertinent cancer susceptibility v2.7 ATRIP Arina Puzriakova Tag watchlist was removed from gene: ATRIP.
Tag Q4_23_promote_green tag was added to gene: ATRIP.
Tag Q4_23_expert_review tag was added to gene: ATRIP.
Breast cancer pertinent cancer susceptibility v2.7 ATRIP Arina Puzriakova commented on gene: ATRIP: As reviewed by Dmitrijs Rots (Children's Clinical University Hospital), the previously mentioned metanalysis paper has now been published (PMID: 37592023). This showed that for cases in the Breast Cancer Association Consortium (BCAC) dataset there were 13 carriers of ATRIP protein-truncating variants variants and 9 carriers in UK Biobank (UKB); in controls there were 3 carriers in BCAC and 57 in UKB (p = 0.000106).

I am uncertain whether this is sufficient evidence to add the ATRIP gene as Green to the panel and therefore this will be flagged for further GMS expert review.
Breast cancer pertinent cancer susceptibility v2.5 ATRIP Dmitrijs Rots reviewed gene: ATRIP: Rating: GREEN; Mode of pathogenicity: Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments; Publications: 37592023; Phenotypes: Breast cancer; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Breast cancer pertinent cancer susceptibility v2.5 CDH1 Arina Puzriakova Publications for gene: CDH1 were set to 36436516
Breast cancer pertinent cancer susceptibility v2.4 CDH1 Arina Puzriakova Phenotypes for gene: CDH1 were changed from Lobular breast cancer to Diffuse gastric and lobular breast cancer syndrome with or without cleft lip and/or palate, OMIM:137215
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Tag Q3_23_promote_green tag was added to gene: CDH1.
Tag Q3_23_expert_review tag was added to gene: CDH1.
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Classified gene: CDH1 as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Added comment: Comment on list classification: New gene added to this panel by Lauma Freimane. Germline heterozygous variants have been found in diffuse gastric and lobular breast cancer syndrome. Patients may develop lobular breast cancer only or lobular breast cancer with gastric cancer. Lobular carcinoma of the breast has been reported in up to 60% of female carriers.

Overall there is sufficient evidence to classify this as a breast cancer susceptibility gene. However, it should be noted that this gene is already covered by a targeted panel, R215 CDH1-related cancer syndrome. Will leave the decision with the GMS expert group as to whether this phenotype should also be covered by this panel.
Breast cancer pertinent cancer susceptibility v2.3 CDH1 Arina Puzriakova Gene: cdh1 has been classified as Amber List (Moderate Evidence).
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova changed review comment from: 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.

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.
-----

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.; to: 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.
-----

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.
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova Classified gene: ATRIP as Amber List (moderate evidence)
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova Added comment: Comment 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.
Breast cancer pertinent cancer susceptibility v2.2 ATRIP Arina Puzriakova Gene: atrip has been classified as Amber List (Moderate Evidence).
Breast cancer pertinent cancer susceptibility v2.1 ATRIP Arina Puzriakova Tag watchlist tag was added to gene: ATRIP.
Breast cancer pertinent cancer susceptibility v2.1 ATRIP Arina Puzriakova commented on gene: ATRIP
Breast cancer pertinent cancer susceptibility v2.1 CDH1 Lauma Freimane gene: CDH1 was added
gene: CDH1 was added to Breast cancer pertinent cancer susceptibility. Sources: Literature
Mode of inheritance for gene: CDH1 was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Publications for gene: CDH1 were set to 36436516
Phenotypes for gene: CDH1 were set to Lobular breast cancer
Review for gene: CDH1 was set to GREEN
Added comment: Sources: Literature
Breast cancer pertinent cancer susceptibility v2.1 ATRIP Lauma Freimane gene: ATRIP was added
gene: ATRIP was added to Breast cancer pertinent cancer susceptibility. Sources: Literature
Mode of inheritance for gene: ATRIP was set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
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
Added comment: 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: Literature
Breast cancer pertinent cancer susceptibility v2.1 Catherine Snow Panel version 2.0 has been signed off on 2023-03-22
Breast cancer pertinent cancer susceptibility v2.0 Catherine Snow promoted panel to version 2.0
Breast cancer pertinent cancer susceptibility v1.8 BRCA1 Arina Puzriakova Tag Q2_22_MOI was removed from gene: BRCA1.
Tag Q2_22_expert_review was removed from gene: BRCA1.
Breast cancer pertinent cancer susceptibility v1.8 BRCA1 Arina Puzriakova commented on gene: BRCA1: The mode of inheritance of this gene has been updated to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.
Breast cancer pertinent cancer susceptibility v1.7 BRCA1 Arina Puzriakova Source NHS GMS was added to BRCA1.
Mode of inheritance for gene BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Breast cancer pertinent cancer susceptibility v1.6 BRCA2 Arina Puzriakova Phenotypes for gene: BRCA2 were changed from Breast cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555; {Breast cancer, male, susceptibility to}, OMIM:114480
Breast cancer pertinent cancer susceptibility v1.5 BRCA1 Arina Puzriakova Tag Q2_22_MOI tag was added to gene: BRCA1.
Tag Q2_22_expert_review tag was added to gene: BRCA1.
Breast cancer pertinent cancer susceptibility v1.5 BRCA1 Arina Puzriakova Added comment: Comment on mode of inheritance: Although more rare, biallelic germline BRCA1 variants have been shown to also confer breast and ovarian cancer susceptibility (with or without FA‐like features), and multiple such cases have been reported worldwide (PMIDs: 23269703; 25472942; 31347298; 33477375).

This may warrant an MOI change from 'monoallelic' to 'both mono- and biallelic' to ensure these rarer cases are not missed; however this will be flagged for further review to confirm whether the GMS expert group agrees with the change.
Breast cancer pertinent cancer susceptibility v1.5 BRCA1 Arina Puzriakova Mode of inheritance for gene: BRCA1 was changed from MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Breast cancer pertinent cancer susceptibility v1.4 BRCA1 Arina Puzriakova Phenotypes for gene: BRCA1 were changed from Breast cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370
Breast cancer pertinent cancer susceptibility v1.2 Catherine Snow Panel types changed to Cancer Germline 100K; GMS Cancer Germline Virtual; GMS signed-off
Panel version 1.1 has been signed off on 2021-09-29
Breast cancer pertinent cancer susceptibility v1.1 PTEN Catherine Snow Classified gene: PTEN as Red List (low evidence)
Breast cancer pertinent cancer susceptibility v1.1 PTEN Catherine Snow Added comment: Comment on list classification: Rating red following review by C Turnball (ICR) of predisposition panels for GMS phase 2 indications.
Breast cancer pertinent cancer susceptibility v1.1 PTEN Catherine Snow Gene: pten has been classified as Red List (Low Evidence).
Breast cancer pertinent cancer susceptibility v1.0 Louise Daugherty promoted panel to version 1.0
Breast cancer pertinent cancer susceptibility Ellen McDonagh approved panel
Breast cancer pertinent cancer susceptibility TP53 Ellen McDonagh classified TP53 as green
Breast cancer pertinent cancer susceptibility TP53 Ellen McDonagh commented on TP53
Breast cancer pertinent cancer susceptibility PTEN Ellen McDonagh classified PTEN as green
Breast cancer pertinent cancer susceptibility PTEN Ellen McDonagh commented on PTEN
Breast cancer pertinent cancer susceptibility PALB2 Ellen McDonagh classified PALB2 as green
Breast cancer pertinent cancer susceptibility PALB2 Ellen McDonagh commented on PALB2
Breast cancer pertinent cancer susceptibility BRCA2 Ellen McDonagh classified BRCA2 as green
Breast cancer pertinent cancer susceptibility BRCA2 Ellen McDonagh commented on BRCA2
Breast cancer pertinent cancer susceptibility BRCA1 Ellen McDonagh classified BRCA1 as green
Breast cancer pertinent cancer susceptibility BRCA1 Ellen McDonagh commented on BRCA1