Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000561973 | SCV000663769 | uncertain significance | Hereditary cancer-predisposing syndrome | 2017-01-12 | criteria provided, single submitter | clinical testing | Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species |
| Baylor Genetics | RCV000195473 | SCV000598657 | likely pathogenic | Fanconi anemia, complementation group O | 2017-08-01 | no assertion criteria provided | clinical testing | This +5 splice variant has been observed in a newborn patient with Fanconi anemia. The diagnosis was confirmed by chromosome breakage analysis. Heterozygous carriers are expected to be asymptomatic carriers |
| Color | RCV000561973 | SCV000691251 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-08-25 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000195473 | SCV000255190 | uncertain significance | Fanconi anemia, complementation group O | 2019-01-10 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 3 of the RAD51C gene. It does not directly change the encoded amino acid sequence of the RAD51C protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs145779113, ExAC 0.03%). This variant has been observed in an individual affected with breast cancer (PMID: 21597919). Additionally, this variant has been reported on the opposite chromosome (in trans) from another variant in RAD51C in an individual with clinical features also observed in Fanconi anemia (PMID: 29278735). ClinVar contains an entry for this variant (Variation ID: 216805). Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of nucleotide changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. 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. |