ClinVar Miner

Submissions for variant NM_033084.5(FANCD2):c.1777C>T (p.Pro593Ser) (rs147523071)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459559 SCV000547226 uncertain significance Fanconi anemia 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 593 of the FANCD2 protein (p.Pro593Ser). The proline residue is weakly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs147523071, ExAC 0.1%). This variant has not been reported in the literature in individuals with FANCD2-related disease. ClinVar contains an entry for this variant (Variation ID: 134313). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine 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.
Fulgent Genetics,Fulgent Genetics RCV000764454 SCV000895516 uncertain significance Fanconi anemia, complementation group D2 2018-10-31 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000764454 SCV000898676 uncertain significance Fanconi anemia, complementation group D2 2018-11-07 criteria provided, single submitter clinical testing FANCD2 NM_033084.4 exon 20 p.Pro593Ser (c.1777C>T): This variant has not been reported in the literature and is present in 0.1% (184/129068) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/3-10103845-C-T). This variant is present in ClinVar (Variation ID:134313). This variant amino acid Serine (Ser) is present in several species including multiple primates and other mammals, and it is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
ITMI RCV000120987 SCV000085155 not provided not specified 2013-09-19 no assertion provided reference population

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