Pigmentary skin disorders

Gene: XRCC2

Green List (high evidence)

Comment on list classification: There are now 3 unrelated individuals with biallelic XRCC2 variants and Fanconi anaemia. All reported patients were homozygous for a recurrent p.(Arg215Ter) variant. Functional evidence is supportive of this gene-disease association. Hence, this gene should be promoted at the next GMS update.

Created: 8 May 2026, 3:23 p.m. | Last Modified: 8 May 2026, 3:23 p.m.

Panel Version: 5.2

PMID: 42071175 Cenciarelli et al., 2026
2 related adult individuals (19yo female and 20yo male) from a consanguineous Egyptian family, homozygous for XRCC2 p.(Arg215Ter). Both patients presented with mild intellectual disability, microcephaly, distinctive facial features, short stature, thumb abnormalities, and abnormal skin pigmentation. DEB test resulted negative in peripheral blood during childhood and no cytopenia, clonal evolution, or other hematological complications were detected. Diagnosed with 'Fanconi anemia-like disorder' without major hematological manifestations.

PMID: 30237576 Maddirevula et al., 2019
Report of a 3 years old Saudi girl, homozygous for XRCC2 c.643C>T:p.(Arg215*), diagnosed with XRCC2-related Fanconi anemia. At birth, she was noted to have borderline microcephaly (OFC was 33 cm); also noted to have bilateral hypoplastic thumb, multiple café late spots, strabismus, and dysmorphic facial features. She developed failure to thrive with progressive microcephaly (at age of 3 years, head circumference was 45 cm. Investigation showed pancytopenia. Chromosomal breakage was 100%. Brain MRI at 3 months of age was unremarkable.
Her parents are second cousins. Sister was similarly affected, died of respiratory failure and pancytopenia.

XRCC2 is putatively associated with AR Fanconi anemia, complementation group U, OMIM:617247 (accessed 8th May 2026). The gene-disease relationship was classified as Limited by ClinGen Hereditary Cancer GCEP in 2023.

Created: 8 May 2026, 3:22 p.m. | Last Modified: 8 May 2026, 3:25 p.m.

Panel Version: 5.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Fanconi anemia, complementation group U, OMIM:617247

Publications

• 42071175
• 30237576

Green List (high evidence)

This gene is an established cause of Fanconi anaemia. PLEASE NOTE - The original lists for Dermatology-related genes for PanelApp provided by myself and John McGrath and myself and Tom Cullup were extensively researched. It would be very helpful if someone at GEL could review those genes which we rated at Green and have not been included as green on PanelApp due to apparent lack of evidence, as it is likely that clinically-relevant well-established diagnoses are being missed by this panel.

Created: 22 Mar 2026, 1:42 p.m. | Last Modified: 22 Mar 2026, 1:42 p.m.

Panel Version: 4.13

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Fanconi anaemia

Publications

• 41526458
• 22232082
• 27208205
• 30042186

I don't know

?Single case in literature. Amber on FA/Bloom syndrome GMS panel

Created: 12 Dec 2019, 12:23 p.m. | Last Modified: 12 Dec 2019, 12:23 p.m.

Panel Version: 0.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
FANCONI ANEMIA, COMPLEMENTATION GROUP U; FANCU

Publications

• 22232082

Green List (high evidence)

Following discussion with the Genomics England clinical team it was agreed that genes associated with Fanconi anaemia should be included on this panel. Therefore added to panel as a Green gene.

Created: 2 Dec 2019, 3:48 p.m. | Last Modified: 2 Dec 2019, 3:48 p.m.

Panel Version: 0.22