ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.3624C>T (p.Ser1208=) (rs149797103)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479566 SCV000567385 uncertain significance not provided 2017-02-21 criteria provided, single submitter clinical testing The c.3624 C>T variant in the FANCA gene has been reported previously in the heterozygous state in patients with Fanconi anemia who were also heterozygous for a second FANCA variant, however, additional clinical and familial segregation information were not included (Gille et al., 2012; Ameziane et al., 2008). This splice site variant destroys the natural splice donor site and creates a cryptic splice donor site in exon 36, and is expected to cause abnormal gene splicing. The c.3624 C>T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret c.3624 C>T as a variant of uncertain significance.
Genetic Services Laboratory,University of Chicago RCV000500885 SCV000594652 likely pathogenic Fanconi anemia, complementation group A 2016-11-11 criteria provided, single submitter clinical testing
Invitae RCV000813304 SCV000953661 likely pathogenic Fanconi anemia 2019-12-13 criteria provided, single submitter clinical testing This sequence change affects codon 1208 of the FANCA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the FANCA protein. This variant is present in population databases (rs149797103, ExAC 0.07%). This variant has been observed in several individuals affected with Fanconi anemia (PMID: 29098742, 17924555, 22778927). ClinVar contains an entry for this variant (Variation ID: 419528). Experimental studies have shown that this change results in aberrant splicing (PMID: 17924555). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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