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| Inherited ovarian cancer (without breast cancer) v2.28 | BRIP1 |
Sarah Leigh changed review comment from: Comment on phenotypes: Association of BRIP1 and breast cancer has been refuted (https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_9910) {Breast cancer, early-onset, susceptibility to}, OMIM:114480;Hereditary breast carcinoma, MONDO:0016419; to: Comment on phenotypes: Association of BRIP1 and breast cancer has been refuted (https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_9910) {Breast cancer, early-onset, susceptibility to}, OMIM:114480;Hereditary breast carcinoma, MONDO:0016419. However, in PMID:31822495 they report very rare BRIP1 missense germline variants (minor allele frequency < 0.0001) in nearly 2% of 2,160 early-onset breast cancer and 1,199 ovarian cancer patients. Functional studies on 20 of these variants revealed 75% resulted in protein hypomorph or null products. The authors also reported that in a clinical cohort of >117,000 breast and ovarian cancer patients, the combined odds ratio associated with BRIP1 hypomorph or null missense carriers compared to the general population was 2.30 (95%CI=1.60-3.30, p<0.0001). |
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| Inherited ovarian cancer (without breast cancer) v2.28 | BRIP1 |
Sarah Leigh changed review comment from: Comment on phenotypes: Association of BRIP1 and breast cancer has been refuted (https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_9910) {Breast cancer, early-onset, susceptibility to}, OMIM:114480;Hereditary breast carcinoma, MONDO:0016419; to: Comment on phenotypes: Association of BRIP1 and breast cancer has been refuted (https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_9910) {Breast cancer, early-onset, susceptibility to}, OMIM:114480;Hereditary breast carcinoma, MONDO:0016419 |
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| Inherited ovarian cancer (without breast cancer) v2.27 | BRIP1 | Sarah Leigh Phenotypes for gene: BRIP1 were changed from ovarian epithelial tumor, MONDO:0002229 to familial ovarian cancer, MONDO:0016248 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.26 | BRIP1 |
Sarah Leigh Added comment: Comment on phenotypes: Association of BRIP1 and breast cancer has been refuted (https://search.clinicalgenome.org/kb/gene-validity/CGGCIEX:assertion_9910) {Breast cancer, early-onset, susceptibility to}, OMIM:114480;Hereditary breast carcinoma, MONDO:0016419 |
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| Inherited ovarian cancer (without breast cancer) v2.26 | BRIP1 | Sarah Leigh Phenotypes for gene: BRIP1 were changed from {Breast cancer, early-onset, susceptibility to}, OMIM:114480; Hereditary breast carcinoma, MONDO:0016419 to ovarian epithelial tumor, MONDO:0002229 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.25 | BRCA1 |
Arina Puzriakova Added comment: Comment on mode of inheritance: Although more rare, biallelic 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). There are at least two unrelated individuals in literature who were diagnosed with ovarian carcinoma in association with biallelic germline BRCA1 variants. 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. |
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| Inherited ovarian cancer (without breast cancer) v2.22 | AR | Arina Puzriakova Phenotypes for gene: AR were changed from Androgen insensitivity, 300068; Spinal and bulbar muscular atrophy of Kennedy, 313200; Androgen insensitivity, partial, with or without breast cancer, 312300; {Prostate cancer, susceptibility to}, 176807; Hypospadias 1, X-linked, 300633 to Androgen insensitivity, OMIM:300068; Androgen insensitivity, partial, with or without breast cancer, OMIM:312300 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.21 | ATM | Arina Puzriakova Phenotypes for gene: ATM were changed from Ataxia-telangiectasia, 208900; Lymphoma, B-cell non-Hodgkin, somatic; {Breast cancer, susceptibility to}, 114480; Lymphoma, mantle cell; T-cell prolymphocytic leukemia, somatic; Breast and Ovarian Cancer to {Breast cancer, susceptibility to}, OMIM:114480 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.20 | MLH1 | Arina Puzriakova changed review comment from: Comment on phenotypes: This gene is also associated with Colorectal cancer, hereditary nonpolyposis, type 2 (MIM# 6093100; Mismatch repair cancer syndrome 1 (MIM# 276300); Muir-Torre syndrome (MIM# 158320); to: Comment on phenotypes: This gene is also associated with Colorectal cancer, hereditary nonpolyposis, type 2 (MIM# 609310); Mismatch repair cancer syndrome 1 (MIM# 276300); Muir-Torre syndrome (MIM# 158320) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.20 | PMS2 | Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Colorectal cancer, hereditary nonpolyposis, type 4 (MIM# 614337); Mismatch repair cancer syndrome 4 (MIM# 619101) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.20 | PMS2 | Arina Puzriakova Phenotypes for gene: PMS2 were changed from Breast and Ovarian Cancer to Ovarian cancer, MONDO:0008170 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.19 | RAD51D | Arina Puzriakova Phenotypes for gene: RAD51D were changed from {Breast-ovarian cancer, familial, susceptibility to, 4}, 614291; Breast and Ovarian Cancer; Breast and Ovarian Cancer Susceptibility to {Breast-ovarian cancer, familial, susceptibility to, 4}, OMIM:614291; Breast-ovarian cancer, familial, susceptibility to, 4, MONDO:0013669 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.17 | RAD51C | Arina Puzriakova Phenotypes for gene: RAD51C were changed from Fanconi anemia, complementation group O, 613390; {Breast-ovarian cancer, familial, susceptibility to, 3}, 613399; Breast and Ovarian Cancer; Breast and Ovarian Cancer Susceptibility to {Breast-ovarian cancer, familial, susceptibility to, 3}, OMIM:613399; Breast-ovarian cancer, familial, susceptibility to, 3, MONDO:0013253 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.15 | MSH6 | Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with {Endometrial cancer, familial} (MIM# 608089); Colorectal cancer, hereditary nonpolyposis, type 5 (MIM# 614350); Mismatch repair cancer syndrome 2 (MIM# 619097) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.15 | MSH6 | Arina Puzriakova Phenotypes for gene: MSH6 were changed from Breast and Ovarian Cancer to Ovarian cancer, MONDO:0008170 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.13 | MSH2 | Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Colorectal cancer, hereditary nonpolyposis, type 1 (MIM# 120435); Mismatch repair cancer syndrome 2 (MIM# 619096); Muir-Torre syndrome (MIM# 158320) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.13 | MSH2 | Arina Puzriakova Phenotypes for gene: MSH2 were changed from Breast and Ovarian Cancer to Ovarian cancer, MONDO:0008170 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.11 | MLH1 | Arina Puzriakova Added comment: Comment on phenotypes: This gene is also associated with Colorectal cancer, hereditary nonpolyposis, type 2 (MIM# 6093100; Mismatch repair cancer syndrome 1 (MIM# 276300); Muir-Torre syndrome (MIM# 158320) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.11 | MLH1 | Arina Puzriakova Phenotypes for gene: MLH1 were changed from Adult Glioma; Colorectal; Endometrial Carcinoma; Hepatopancreatobiliary; Ovarian to Ovarian cancer, MONDO:0008170 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.9 | BRIP1 | Arina Puzriakova Phenotypes for gene: BRIP1 were changed from ?Breast cancer, early-onset, 114480; Fanconi anemia, complementation group J, 609054; Breast and Ovarian Cancer; Breast Cancer to {Breast cancer, early-onset, susceptibility to}, OMIM:114480; Hereditary breast carcinoma, MONDO:0016419 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.7 | BRCA2 | Arina Puzriakova Phenotypes for gene: BRCA2 were changed from {Breast-ovarian cancer, familial, 2}, 612555; Fanconi anemia, complementation group D1, 605724; Prostate cancer, 176807; {Breast cancer, male, susceptibility to}, 114480; Wilms tumor, 194070; {Medulloblastoma}, 155255; {Glioblastoma 3},; Hereditary Breast and Ovarian Cancer ; Hereditary Breast and Ovarian Cancer Syndrome; Breast and Ovarian Cancer; High Risk Breast Cancer ; Breast cancer to {Breast-ovarian cancer, familial, 2}, OMIM:612555; Hereditary breast ovarian cancer syndrome, MONDO:0003582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.6 | BRCA1 | Arina Puzriakova Phenotypes for gene: BRCA1 were changed from {Breast-ovarian cancer, familial, 1}, 604370; {Pancreatic cancer, susceptibility to, 4}, 614320; Hereditary Breast and Ovarian Cancer ; Hereditary Breast and Ovarian Cancer Syndrome; Breast and Ovarian Cancer; High Risk Breast Cancer ; Breast cancer to {Breast-ovarian cancer, familial, 1}, OMIM:604370; Hereditary breast ovarian cancer syndrome, MONDO:0003582 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.5 | PALB2 | Arina Puzriakova changed review comment from: Comment on list classification: Kept rating Red, as it remains unclear whether the risk is sufficiently high to warrant the inclusion of PALB2 in the ovarian cancer gene panel.; to: Comment on list classification: Kept rating Red, but this gene will be flagged for review (added 'for-review' tag) at the next GMS panel update to assess whether the risk is sufficiently high to warrant inclusion of PALB2 on the ovarian cancer gene panel in the context of two recent publications (PMIDs: 31841383 and 32546565) identified by the expert reviewer. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.5 | PALB2 |
marc tischkowitz commented on gene: PALB2: From the key paper (Yang 2020): Table 3 - 16% risk to age 80 ( 95% CI 8-28%) if 2 first degree relatives affected at age 50, 11% risk to age 80 (95% CI 6-21) if mother and maternal grandmother diagnosed at age 50. Therefore clinically actionable if there is a strong family history. This paper and that of Song 2020 supersede previous published studies which are based on many fewer cases. |
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| Inherited ovarian cancer (without breast cancer) v2.4 | PALB2 | Arina Puzriakova Added comment: Comment on list classification: Kept rating Red, as it remains unclear whether the risk is sufficiently high to warrant the inclusion of PALB2 in the ovarian cancer gene panel. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v2.3 | PALB2 | marc tischkowitz reviewed gene: PALB2: 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: PMID: 31841383: PMID: 32546565; Phenotypes: breast cancer, ovarian cancer, pancreatic cancer; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted; Current diagnostic: yes | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v1.10 | Ivone Leong Panel types changed to Rare Disease 100K; GMS Rare Disease; GMS signed-off | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v1.9 | Ivone Leong List of related panels changed from Familial ovarian cancer to Familial ovarian cancer; R207 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) v1.2 |
Ellen McDonagh Panel name changed from Familial ovarian cancer to Inherited ovarian cancer (without breast cancer) List of related panels changed from to Familial ovarian cancer Panel types changed to Rare Disease 100K; GMS Rare Disease |
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| Inherited ovarian cancer (without breast cancer) | MSH2 | Ellen McDonagh marked MSH2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | MSH2 | Ellen McDonagh marked MSH2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | MSH6 | Ellen McDonagh marked MSH6 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | RAD51C | Ellen McDonagh marked RAD51C as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | RAD51D | Ellen McDonagh marked RAD51D as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | MLH1 | Ellen McDonagh marked MLH1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | BRIP1 | Ellen McDonagh marked BRIP1 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Inherited ovarian cancer (without breast cancer) | BRCA2 | Ellen McDonagh marked BRCA2 as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||