Severe microcephaly

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

3 reviews

Louise Daugherty (Genomics England Curator)

I don't know

As discussed with the GMS Neurology Specialist Test Group webex call 11thJuly 2019: The Specialist Test Group all agreed that there is only enough evidence to rate this gene Red
Created: 29 Jul 2019, 4:18 p.m. | Last Modified: 29 Jul 2019, 4:18 p.m.
Panel Version: 1.62

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, 2:30 p.m.

Publications

Rebecca Foulger (Genomics England curator)

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, 11:35 a.m.

Details

Mode of Inheritance
BIALLELIC, autosomal or pseudoautosomal
Sources
  • NHS GMS
  • Expert Review Red
  • Other
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

29 Jul 2019, Gel status: 1

Added New Source

Louise Daugherty (Genomics England Curator)

Source NHS GMS was added to FANCM.

2 Mar 2017, Gel status: 1

panel promoted to version 1

Rebecca Foulger (Genomics England curator)

2nd March 2017: Panel review was assessed and panel was revised according to expert review and additional curation. This panel began with an expert gene list from Professor Andrew Jackson (University of Edinburgh) for primary microcephaly (MCPH) and microcephalic primordial dwarfism (MPD). Other disorders are included where microcephaly is a primary feature. Disorders where microcephaly is not the primary presenting feature are not included (e.g. congenital disorders of glycosylation, Proud syndrome, Norrie disease). The panel does not include disorders with a cortical malformation (e.g. lissencephaly) since the Malformations of cortical development' panel would be applied to these patients.

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).

30 Jan 2017, Gel status: 4

Added New Source

Rebecca Foulger (Genomics England curator)

FANCM was added to Primary Microcephaly - Microcephalic Dwarfism Spectrumpanel. Sources: Other, Expert Review Green

30 Jan 2017, Gel status: 0

Created

Rebecca Foulger (Genomics England curator)

FANCM was created by rfoulger