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Confirmed Fanconi anaemia or Bloom syndrome v2.9 RAD51C Achchuthan Shanmugasundram Mode of inheritance for gene: RAD51C was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Confirmed Fanconi anaemia or Bloom syndrome v2.8 RAD51C Ida Ertmanska changed review comment from: Comment on list classification: There are two biallelic and two monoallelic cases reported with Fanconi anemia (or FA-like disorder). RAD51C should remain Amber for Confirmed Fanconi anaemia or Bloom syndrome, until more evidence emerges.; to: Comment on list classification: There are two biallelic and two monoallelic cases reported with Fanconi anemia (or FA-like disorder). RAD51C should remain Amber for Confirmed Fanconi anaemia or Bloom syndrome, until more evidence emerges. The MOI should be set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal.
Confirmed Fanconi anaemia or Bloom syndrome v2.8 RAD51C Ida Ertmanska changed review comment from: PMID: 29278735 Jacquinet et al., 2018
Report of a newborn female with an expanded phenotype of Fanconi anemia, complementation group O (FANCO). Prenatal trio exome seq detected compound heterozygous variants in RAD51C NM_058216.2: c.935G>A (p.Arg312Gln) and c.571+5G>A. Diagnosed prenatally with several congenital anomalies. Chromosome breakage studies confirmed the diagnosis of FANCO, with expanded phenotype of cleft lip and palate and lobar holoprosencephaly. The patient died shortly after birth.
Functional: PMID: 37031326 Zemet et al., 2023 - trio WGS studies in the same family as PMID: 29278735 revealed SNV hypermutagenesis.

PMID: 26681308 Ameziane et al., 2015
Report of a de novo heterozygous RAD51C variant g.41022153G>A; p.Ala293Thr (NM_002875). The atypical FA-like individual presented at 2.5 years of age with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle. A positive DNA cross-linker (DEB)-induced chromosomal breakage test confirmed the suspicion of FA. Lack of typical bone marrow failure and malignancies at age 23yrs.

PMID: 26253028 Wang et al., 2015
1yo girl born with radial dysplasia, absent right thumb, pelvic left kidney and increased DNA damage sensitivity, including the appearance of radial chromosomes in peripheral blood lymphoblasts and skin fibroblasts after treatment with diepoxybutane (DEB) and mitomycin C (MMC); diagnosed with Fanconi Anemia. WES revealed a de novo heterozygous mutation in RAD51: c.391A>C.

PMID: 20400963 Vaz et al., 2010
Consanguineous Pakistani family; 3 siblings with extensive congenital anomalies, diagnosed with FA-like disorder, homozygous for c.773G>A, p.Arg258His in RAD51C. Individual IV-2 died at 2 days old, IV-3 died at age 2 months, IV-5 (also affected) was 10 years old at time of report and did not develop cancer or hematological abnormalities. Parents confirmed heterozygous, unaffected sibling IV-1 was homozygous for WT allele. Functional: G2 arrest in fibroblasts of affected individual IV-5 was rescued by injection of WT RAD51C.

Functional evidence:
PMID: 36906610 Tomaszowski et al., 2023 - 'Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress' - interestingly, single gene knockouts of either Brca2 or Rad51c did not result in a Fanconi anemia phenotype in the mice.

This gene is associated with AR Fanconi anemia, complementation group O, MIM:613390 and {Breast-ovarian cancer, familial, susceptibility to, 3}, MIM:613399 (OMIM accessed 9th Jan 2025). ClinGen classified the association between RAD51C and AR Fanconi anemia as Limited in 2023.; to: PMID: 29278735 Jacquinet et al., 2018
Report of a newborn female with an expanded phenotype of Fanconi anemia, complementation group O (FANCO). Prenatal trio exome seq detected compound heterozygous variants in RAD51C NM_058216.2: c.935G>A (p.Arg312Gln) and c.571+5G>A. Diagnosed prenatally with several congenital anomalies. Chromosome breakage studies confirmed the diagnosis of FANCO, with expanded phenotype of cleft lip and palate and lobar holoprosencephaly. The patient died shortly after birth.
Functional: PMID: 37031326 Zemet et al., 2023 - trio WGS studies in the same family as PMID: 29278735 revealed SNV hypermutagenesis.

PMID: 26681308 Ameziane et al., 2015
Report of a de novo heterozygous RAD51C variant g.41022153G>A; p.Ala293Thr (NM_002875). The atypical FA-like individual presented at 2.5 years of age with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle. A positive DNA cross-linker (DEB)-induced chromosomal breakage test confirmed the suspicion of FA. Lack of typical bone marrow failure and malignancies at age 23yrs.

PMID: 26253028 Wang et al., 2015
1yo girl born with radial dysplasia, absent right thumb, pelvic left kidney and increased DNA damage sensitivity, including the appearance of radial chromosomes in peripheral blood lymphoblasts and skin fibroblasts after treatment with diepoxybutane (DEB) and mitomycin C (MMC); diagnosed with Fanconi Anemia. WES revealed a de novo heterozygous mutation in RAD51: c.391A>C.

PMID: 20400963 Vaz et al., 2010
Consanguineous Pakistani family; 3 siblings with extensive congenital anomalies, diagnosed with FA-like disorder, homozygous for c.773G>A, p.Arg258His in RAD51C. Individual IV-2 died at 2 days old, IV-3 died at age 2 months, IV-5 (also affected) was 10 years old at time of report and did not develop cancer or hematological abnormalities. Parents confirmed heterozygous, unaffected sibling IV-1 was homozygous for WT allele. Functional: G2 arrest in fibroblasts of affected individual IV-5 was rescued by injection of WT RAD51C.

Functional evidence:
PMID: 36906610 Tomaszowski et al., 2023 - 'Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress' - interestingly, single gene knockouts of either Brca2 or Rad51c did not result in a Fanconi anemia phenotype in the mice.

This gene is associated with AR Fanconi anemia, complementation group O, MIM:613390 and {Breast-ovarian cancer, familial, susceptibility to, 3}, MIM:613399 (OMIM accessed 9th Jan 2025). ClinGen classified the association between RAD51C and AR Fanconi anemia as Limited in 2023.
Confirmed Fanconi anaemia or Bloom syndrome v2.8 RAD51C Ida Ertmanska edited their review of gene: RAD51C: Changed mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Confirmed Fanconi anaemia or Bloom syndrome v2.8 RAD51C Achchuthan Shanmugasundram Phenotypes for gene: RAD51C were changed from Fanconi anemia, complementation group O, 613390; 613390 Fanconi anemia, complementation group O to Fanconi anemia, complementation group O, OMIM:613390; Fanconi anemia complementation group O, MONDO:0013248
Confirmed Fanconi anaemia or Bloom syndrome v2.7 RAD51C Ida Ertmanska commented on gene: RAD51C: Comment on list classification: There are two biallelic and two monoallelic cases reported with Fanconi anemia (or FA-like disorder). RAD51C should remain Amber for Confirmed Fanconi anaemia or Bloom syndrome, until more evidence emerges.
Confirmed Fanconi anaemia or Bloom syndrome v2.7 RAD51C Ida Ertmanska changed review comment from: PMID: 29278735 Jacquinet et al., 2018
Report of a newborn female with an expanded phenotype of Fanconi anemia, complementation group O (FANCO). Prenatal trio exome seq detected compound heterozygous variants in RAD51C NM_058216.2: c.935G>A (p.Arg312Gln) and c.571+5G>A. Diagnosed prenatally with several congenital anomalies. Chromosome breakage studies confirmed the diagnosis of FANCO, with expanded phenotype of cleft lip and palate and lobar holoprosencephaly. The patient died shortly after birth.
Functional: PMID: 37031326 Zemet et al., 2023 - trio WGS studies in the same family as PMID: 29278735 revealed SNV hypermutagenesis.

PMID: 26681308 Ameziane et al., 2015
Report of a de novo heterozygous RAD51C variant g.41022153G>A; p.Ala293Thr (NM_002875). The atypical FA-like individual presented at 2.5 years of age with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle. A positive DNA cross-linker (DEB)-induced chromosomal breakage test confirmed the suspicion of FA. Lack of typical bone marrow failure and malignancies at age 23yrs.

PMID: 26253028 Wang et al., 2015
1yo girl born with radial dysplasia, absent right thumb, pelvic left kidney and increased DNA damage sensitivity, including the appearance of radial chromosomes in peripheral blood lymphoblasts and skin fibroblasts after treatment with diepoxybutane (DEB) and mitomycin C (MMC); diagnosed with Fanconi Anemia. WES revealed a de novo heterozygous mutation in RAD51: c.391A>C.

PMID: 20400963 Vaz et al., 2010
Consanguineous Pakistani family; 3 siblings with extensive congenital anomalies, diagnosed with FA-like disorder, homozygous for c.773G>A, p.Arg258His in RAD51C. Individual IV-2 died at 2 days old, IV-3 died at age 2 months, IV-5 (also affected) was 10 years old at time of report and did not develop cancer or hematological abnormalities. Parents confirmed heterozygous, unaffected sibling IV-1 was homozygous for WT allele. Functional: G2 arrest in fibroblasts of affected individual IV-5 was rescued by injection of WT RAD51C.

This gene is associated with AR Fanconi anemia, complementation group O, MIM:613390 and {Breast-ovarian cancer, familial, susceptibility to, 3}, MIM:613399 (OMIM accessed 9th Jan 2025). ClinGen classified the association between RAD51C and AR Fanconi anemia as Limited in 2023.; to: PMID: 29278735 Jacquinet et al., 2018
Report of a newborn female with an expanded phenotype of Fanconi anemia, complementation group O (FANCO). Prenatal trio exome seq detected compound heterozygous variants in RAD51C NM_058216.2: c.935G>A (p.Arg312Gln) and c.571+5G>A. Diagnosed prenatally with several congenital anomalies. Chromosome breakage studies confirmed the diagnosis of FANCO, with expanded phenotype of cleft lip and palate and lobar holoprosencephaly. The patient died shortly after birth.
Functional: PMID: 37031326 Zemet et al., 2023 - trio WGS studies in the same family as PMID: 29278735 revealed SNV hypermutagenesis.

PMID: 26681308 Ameziane et al., 2015
Report of a de novo heterozygous RAD51C variant g.41022153G>A; p.Ala293Thr (NM_002875). The atypical FA-like individual presented at 2.5 years of age with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle. A positive DNA cross-linker (DEB)-induced chromosomal breakage test confirmed the suspicion of FA. Lack of typical bone marrow failure and malignancies at age 23yrs.

PMID: 26253028 Wang et al., 2015
1yo girl born with radial dysplasia, absent right thumb, pelvic left kidney and increased DNA damage sensitivity, including the appearance of radial chromosomes in peripheral blood lymphoblasts and skin fibroblasts after treatment with diepoxybutane (DEB) and mitomycin C (MMC); diagnosed with Fanconi Anemia. WES revealed a de novo heterozygous mutation in RAD51: c.391A>C.

PMID: 20400963 Vaz et al., 2010
Consanguineous Pakistani family; 3 siblings with extensive congenital anomalies, diagnosed with FA-like disorder, homozygous for c.773G>A, p.Arg258His in RAD51C. Individual IV-2 died at 2 days old, IV-3 died at age 2 months, IV-5 (also affected) was 10 years old at time of report and did not develop cancer or hematological abnormalities. Parents confirmed heterozygous, unaffected sibling IV-1 was homozygous for WT allele. Functional: G2 arrest in fibroblasts of affected individual IV-5 was rescued by injection of WT RAD51C.

Functional evidence:
PMID: 36906610 Tomaszowski et al., 2023 - 'Hypomorphic Brca2 and Rad51c double mutant mice display Fanconi anemia, cancer and polygenic replication stress' - interestingly, single gene knockouts of either Brca2 or Rad51c did not result in a Fanconi anemia phenotype in the mice.

This gene is associated with AR Fanconi anemia, complementation group O, MIM:613390 and {Breast-ovarian cancer, familial, susceptibility to, 3}, MIM:613399 (OMIM accessed 9th Jan 2025). ClinGen classified the association between RAD51C and AR Fanconi anemia as Limited in 2023.
Confirmed Fanconi anaemia or Bloom syndrome v2.7 RAD51C Ida Ertmanska changed review comment from: PMID: 29278735 Jacquinet et al., 2018
Report of a newborn female with an expanded phenotype of Fanconi anemia, complementation group O (FANCO). Prenatal trio exome seq detected compound heterozygous variants in RAD51C NM_058216.2: c.935G>A (p.Arg312Gln) and c.571+5G>A. Diagnosed prenatally with several congenital anomalies. Chromosome breakage studies confirmed the diagnosis of FANCO, with expanded phenotype of cleft lip and palate and lobar holoprosencephaly. The patient died shortly after birth.
Functional: PMID: 37031326 Zemet et al., 2023 - trio WGS studies in the same family as PMID: 29278735 revealed SNV hypermutagenesis.

PMID: 26681308 Ameziane et al., 2015
Report of a de novo heterozygous RAD51C variant g.41022153G>A; p.Ala293Thr (NM_002875). The atypical FA-like individual presented at 2.5 years of age with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle. A positive DNA cross-linker (DEB)-induced chromosomal breakage test confirmed the suspicion of FA. Lack of typical bone marrow failure and malignancies at age 23yrs.

PMID: 20400963 Vaz et al., 2010
Consanguineous Pakistani family; 3 siblings with extensive congenital anomalies, diagnosed with FA-like disorder, homozygous for c.773G>A, p.Arg258His in RAD51C. Individual IV-2 died at 2 days old, IV-3 died at age 2 months, IV-5 (also affected) was 10 years old at time of report and did not develop cancer or hematological abnormalities. Parents confirmed heterozygous, unaffected sibling IV-1 was homozygous for WT allele. Functional: G2 arrest in fibroblasts of affected individual IV-5 was rescued by injection of WT RAD51C.

This gene is associated with AR Fanconi anemia, complementation group O, MIM:613390 and {Breast-ovarian cancer, familial, susceptibility to, 3}, MIM:613399 (OMIM accessed 9th Jan 2025).; to: PMID: 29278735 Jacquinet et al., 2018
Report of a newborn female with an expanded phenotype of Fanconi anemia, complementation group O (FANCO). Prenatal trio exome seq detected compound heterozygous variants in RAD51C NM_058216.2: c.935G>A (p.Arg312Gln) and c.571+5G>A. Diagnosed prenatally with several congenital anomalies. Chromosome breakage studies confirmed the diagnosis of FANCO, with expanded phenotype of cleft lip and palate and lobar holoprosencephaly. The patient died shortly after birth.
Functional: PMID: 37031326 Zemet et al., 2023 - trio WGS studies in the same family as PMID: 29278735 revealed SNV hypermutagenesis.

PMID: 26681308 Ameziane et al., 2015
Report of a de novo heterozygous RAD51C variant g.41022153G>A; p.Ala293Thr (NM_002875). The atypical FA-like individual presented at 2.5 years of age with growth retardation, microcephaly, hydrocephalus, skeletal (thumb and radius) abnormalities, imperforate anus and an improperly formed left testicle. A positive DNA cross-linker (DEB)-induced chromosomal breakage test confirmed the suspicion of FA. Lack of typical bone marrow failure and malignancies at age 23yrs.

PMID: 26253028 Wang et al., 2015
1yo girl born with radial dysplasia, absent right thumb, pelvic left kidney and increased DNA damage sensitivity, including the appearance of radial chromosomes in peripheral blood lymphoblasts and skin fibroblasts after treatment with diepoxybutane (DEB) and mitomycin C (MMC); diagnosed with Fanconi Anemia. WES revealed a de novo heterozygous mutation in RAD51: c.391A>C.

PMID: 20400963 Vaz et al., 2010
Consanguineous Pakistani family; 3 siblings with extensive congenital anomalies, diagnosed with FA-like disorder, homozygous for c.773G>A, p.Arg258His in RAD51C. Individual IV-2 died at 2 days old, IV-3 died at age 2 months, IV-5 (also affected) was 10 years old at time of report and did not develop cancer or hematological abnormalities. Parents confirmed heterozygous, unaffected sibling IV-1 was homozygous for WT allele. Functional: G2 arrest in fibroblasts of affected individual IV-5 was rescued by injection of WT RAD51C.

This gene is associated with AR Fanconi anemia, complementation group O, MIM:613390 and {Breast-ovarian cancer, familial, susceptibility to, 3}, MIM:613399 (OMIM accessed 9th Jan 2025). ClinGen classified the association between RAD51C and AR Fanconi anemia as Limited in 2023.
Confirmed Fanconi anaemia or Bloom syndrome v2.7 RAD51C Ida Ertmanska Publications for gene: RAD51C were set to 20400963; 22232082
Confirmed Fanconi anaemia or Bloom syndrome v2.6 RAD51C Ida Ertmanska reviewed gene: RAD51C: Rating: AMBER; Mode of pathogenicity: None; Publications: 20400963, 26681308, 29278735, 37031326; Phenotypes: Fanconi anemia, complementation group O, OMIM:613390, Fanconi anemia complementation group O, MONDO:0013248; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty changed review comment from: Discrepant reviews for RAD51C : 1 GLH GREEN (YNEGLH), 3 GLH AMBER (WWMGLH, NWGLH, LSGLH). To be discussed at July workshop to agree rating.; to: Discrepant reviews for RAD51C : 1 GLH GREEN (YNEGLH), 3 GLH AMBER (WWMGLH, NWGLH, LSGLH). To be discussed at July workshop to agree rating.
NWGLH: GREEN/AMBER – would go with the consensus
LSGLH: AMBER – one family reported
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty Classified gene: RAD51C as Amber List (moderate evidence)
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty Added comment: Comment on list classification: As discussed with the GMS Haematology Specialist Test Group at workshop 2nd July 2019. All agreed that there is only enough evidence to rate this gene Amber.
Confirmed Fanconi anaemia or Bloom syndrome v0.27 RAD51C Louise Daugherty Gene: rad51c has been classified as Amber List (Moderate Evidence).
Confirmed Fanconi anaemia or Bloom syndrome v0.26 RAD51C Louise Daugherty commented on gene: RAD51C: Discrepant reviews for RAD51C : 1 GLH GREEN (YNEGLH), 3 GLH AMBER (WWMGLH, NWGLH, LSGLH). To be discussed at July workshop to agree rating.
Confirmed Fanconi anaemia or Bloom syndrome v0.20 RAD51C Louise Daugherty commented on gene: RAD51C: Initial gene list (Consensus Genes for SPEC HAEM Panels 31.01.19 North West v1 FINAL.xlsx) collated by Steve Keeney Molecular Diagnostics Centre Central Manchester NHS Foundation Trust January 2019 on behalf of North West GLH for the GMS Haematology specialist test group. Gene Symbol submitted: RAD51C; Suggested initial gene rating: I don't know; Are variants in this gene part of your current diagnostic practice? No; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: Fanconi anemia, complementation group O 613390; PMID(s): none submitted
Confirmed Fanconi anaemia or Bloom syndrome v0.19 RAD51C Steve Keeney reviewed gene: RAD51C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: Fanconi anemia, complementation group O, 613390; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Confirmed Fanconi anaemia or Bloom syndrome v0.18 RAD51C Louise Daugherty Added phenotypes Fanconi anemia, complementation group O, 613390 for gene: RAD51C
Confirmed Fanconi anaemia or Bloom syndrome v0.16 RAD51C Louise Daugherty Source North West GLH was added to RAD51C.
Confirmed Fanconi anaemia or Bloom syndrome v0.11 RAD51C Louise Daugherty commented on gene: RAD51C: Initial gene list (Consensus Genes for Panels_Haem_SHEFFIELD-29.01.2019.xlsx) collated by Mandy Nesbitt Sheffield Diagnostic Genetics Service, Sheffield Children's NHS Trust January 2019 on behalf of Yorkshire and North East GLH for the GMS Haematology specialist test group. Gene Symbol submitted: RAD51C; Suggested intial gene rating: Green List (high evidence); Are variants in this gene part of your current diagnostic practice? Yes; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Phenotypes: 613390 Fanconi anemia, complementation group O; PMID(s): none submitted
Confirmed Fanconi anaemia or Bloom syndrome v0.10 RAD51C Mandy nesbitt reviewed gene: RAD51C: Rating: GREEN; Mode of pathogenicity: ; Publications: ; Phenotypes: 613390 Fanconi anemia, complementation group O; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal; Current diagnostic: yes
Confirmed Fanconi anaemia or Bloom syndrome v0.9 RAD51C Louise Daugherty Added phenotypes 613390 Fanconi anemia, complementation group O for gene: RAD51C
Confirmed Fanconi anaemia or Bloom syndrome v0.7 RAD51C Louise Daugherty Source Yorkshire and North East GLH was added to RAD51C.
Confirmed Fanconi anaemia or Bloom syndrome v0.6 RAD51C Louise Daugherty reviewed gene: RAD51C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Confirmed Fanconi anaemia or Bloom syndrome v0.5 RAD51C Carl Fratter reviewed gene: RAD51C: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Confirmed Fanconi anaemia or Bloom syndrome v0.4 RAD51C Louise Daugherty Source NHS GMS was added to RAD51C.
Confirmed Fanconi anaemia or Bloom syndrome v0.3 RAD51C Louise Daugherty Source Expert Review Amber was added to RAD51C.
Mode of inheritance for gene RAD51C was changed from to BIALLELIC, autosomal or pseudoautosomal
Added phenotypes Fanconi anemia, complementation group O, 613390 for gene: RAD51C
Publications for gene RAD51C were changed from to 20400963; 22232082
Rating Changed from Red List (low evidence) to Amber List (moderate evidence)
Confirmed Fanconi anaemia or Bloom syndrome v0.2 RAD51C Louise Daugherty gene: RAD51C was added
gene: RAD51C was added to Confirmed Fanconi anaemia or Bloom syndrome. Sources: Wessex and West Midlands GLH
Mode of inheritance for gene: RAD51C was set to