Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001384478 | SCV001583983 | pathogenic | not provided | 2020-06-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in USB1 are known to be pathogenic (PMID: 20817924, 25044170). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 21271650). This variant has been observed in individual(s) with poikiloderma with neutropenia (PMID: 21271650, 21967010). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 496754). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 2 of the USB1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000599282 | SCV005040434 | pathogenic | Poikiloderma with neutropenia | 2024-03-04 | criteria provided, single submitter | clinical testing | Variant summary: USB1 c.266-1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 3' acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Clericuzio_2011). The variant was absent in 251484 control chromosomes (gnomAD). c.266-1G>A has been reported in the literature in individuals affected with Poikiloderma With Neutropenia (example: Clericuzio_2011, Rattanavalai_2012). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 21271650, 21967010). ClinVar contains an entry for this variant (Variation ID: 496754). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Gene |
RCV000599282 | SCV000700243 | not provided | Poikiloderma with neutropenia | no assertion provided | literature only | ||
| OMIM | RCV000599282 | SCV001981671 | pathogenic | Poikiloderma with neutropenia | 2021-10-20 | no assertion criteria provided | literature only |