Radial dysplasia

Gene: FANCM

Red List (low evidence)

FANCM (Fanconi anemia complementation group M)
EnsemblGeneIds (GRCh38): ENSG00000187790
EnsemblGeneIds (GRCh37): ENSG00000187790
OMIM: 609644, Gene2Phenotype
FANCM is in 16 panels

4 reviews

Ellen McDonagh (Genomics England Curator)

Publication PMID: 28837162 entitled: “Individuals with FANCM biallelic mutations do not develop Fanconi anemia, but show risk for breast cancer, chemotherapy toxicity and may display chromosome fragility.” In this study breast cancer probands were investigated for DNA damage response genes, and 5 cases had FANCM loss-of-function variants. They showed a heterogeneous phenotype including cancer predisposition, toxicity to chemotherapy, early menopause, and possibly chromosome fragility. The phenotype severity might correlate with mutation position in the gene. They authors conclude: “Our data indicate that biallelic FANCM mutations do not cause classical FA, providing proof that FANCM is not a canonical FA gene. Moreover, our observations support previous findings suggesting that FANCM is a breast cancer-predisposing gene. Mutation testing of FANCM might be considered for individuals with the above-described clinical features.”
Created: 2 Nov 2017, 2:31 p.m.

Publications

Helen Brittain (Genomics England Curator)

Red List (low evidence)

Comment when marking as ready: Evidence not reached at present for causation. Therefore red.
Created: 11 May 2017, 11:58 a.m.
Comment when marking as ready: Insufficient evidence at present for causation in isolation
Created: 28 Feb 2017, 1:41 p.m.
Comment on list classification: See reviews for discussion of relative evidence for and against causation. The consensus on discussion amongst curation team was that the evidence presented suggests perhaps digenic contribution (FANCA / FANCM) in a patient. Therefore evidence not considered sufficient for inclusion. Await further reports.
Created: 28 Feb 2017, 1:40 p.m.
No current OMIM associated phenotype. Please see comprehensive assessment of the current evidence by Rebecca Foulger. In addition email correspondence with Noemi Roy, who has discussed with Inderjeet Dokal, an expert in this condition and the genes that are thought to be involved. He is aware of one family with compound het mutations in FANCM and FANCA.

It is possible that this gene is related to Fanconi anaemia but based upon the current evidence in my opinion it cannot be included for useful filtering of variants on a diagnostic basis unless further evidence of causation is identified.
Created: 28 Feb 2017, 9:51 a.m.

Mode of inheritance
Unknown

Publications

Rebecca Foulger (Genomics England curator)

Comment on phenotypes: Removed 'Fanconi anemia, complementation group M, 614087' phenotype since MIM:614087 is no longer valid.
Created: 9 Feb 2017, 11:38 a.m.
Comment on list classification: Changed rating from Green to Red based on more recent evidence which disputes that FANCM is a Fanconi anemia gene (Singh et al., 2009 (PMID:19423727) and Lim et al., 2014 (PMID:25078778).
Created: 9 Feb 2017, 11:37 a.m.

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anemia

Publications

Variants in this GENE are reported as part of current diagnostic practice

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • Illumina TruGenome Clinical Sequencing Services
  • Radboud University Medical Center, Nijmegen
  • UKGTN
  • Eligibility statement prior genetic testing
Phenotypes
  • Fanconi Anemia
OMIM
609644
Clinvar variants
Variants in FANCM
Penetrance
Complete
Publications
  • 16116422 Meetei et al., 2005 paper that originally classified FANCM as a Fanconi anemia gene
  • 19423727 Singh et al., 2009 reclassified the Meetei et al, patients as having FANCA
  • 25078778 Lim et al., 2014 did NOT find evidence to support FANCM as a gene associated with Fanconi anemia.
Panels with this gene

History Filter Activity

23 May 2017, Gel status: 1

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

23.05.2017: Panel revised and approved to Version 1.0 after expert review.

11 May 2017, Gel status: 1

Gene classified by Genomics England curator

Helen Brittain (Genomics England Curator)

This gene has been classified as Red List (Low Evidence).

9 Feb 2017, Gel status: 1

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for FANCM were set to Fanconi Anemia

9 Feb 2017, Gel status: 1

Set publications

Rebecca Foulger (Genomics England curator)

Publications for FANCM were set to 16116422 Meetei et al., 2005 paper that originally classified FANCM as a Fanconi anemia gene; 19423727 Singh et al., 2009 reclassified the Meetei et al, patients as having FANCA; 25078778 Lim et al., 2014 did NOT find evidence to support FANCM as a gene associated with Fanconi anemia.

9 Feb 2017, Gel status: 1

Gene classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

This gene has been classified as Red List (Low Evidence).

18 Oct 2016, Gel status: 3

Set Mode of Inheritance, Added New Source

Rebecca Foulger (Genomics England curator)

FANCM was added to Radial dysplasiapanel. Source: Illumina TruGenome Clinical Sequencing Services Model of inheritance for gene FANCM was set to BIALLELIC, autosomal or pseudoautosomal

18 Oct 2016, Gel status: 2

Added New Source

Rebecca Foulger (Genomics England curator)

FANCM was added to Radial dysplasiapanel. Source: Radboud University Medical Center, Nijmegen

18 Oct 2016, Gel status: 1

Added New Source

Rebecca Foulger (Genomics England curator)

FANCM was added to Radial dysplasiapanel. Source: UKGTN

18 Oct 2016, Gel status: 0

Added New Source

Rebecca Foulger (Genomics England curator)

FANCM was added to Radial dysplasiapanel. Sources: Eligibility statement prior genetic testing

18 Oct 2016, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

FANCM was created by rfoulger