Submissions for variant NM_000135.4(FANCA):c.775C>G (p.Pro259Ala)

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Total submissions: 1

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001059113	SCV001223722	uncertain significance	Fanconi anemia	2019-11-26	criteria provided, single submitter	clinical testing	This sequence change replaces proline with alanine at codon 259 of the FANCA protein (p.Pro259Ala). The proline residue is weakly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs200988394, ExAC 0.004%). This variant has not been reported in the literature in individuals with FANCA-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The alanine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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