Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002469289 | SCV002766284 | uncertain significance | not specified | 2022-11-22 | criteria provided, single submitter | clinical testing | Variant summary: CSF1R c.1859-119G>A is located at a position not widely known to affect splicing. However, several computational tools predict a significant impact on normal splicing: Four predict the variant creates a cryptic 3 acceptor site. At least one publication reports experimental evidence that this variant results in creating a cryptic 3 acceptor site and having a 117-bp insertion into the open reading frame, thus leading to an elongated protein p.Ser620delins40, the inserted fragment is an extension of exon 14 to intron 13 and begins just after c.1859-119G>A (Guo_2019). The variant was absent in 31386 control chromosomes (gnomAD). c.1859-119G>A has been reported in the literature in a compound heterozygous individual affected with Brain Abnormalities, Neurodegeneration, And Dysosteosclerosis (Guo_2019). However, these data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| OMIM | RCV000785986 | SCV000924616 | pathogenic | Brain abnormalities, neurodegeneration, and dysosteosclerosis | 2019-06-21 | no assertion criteria provided | literature only |