Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000689685 | SCV000817348 | pathogenic | Exostoses, multiple, type 2 | 2018-06-19 | criteria provided, single submitter | clinical testing | This variant has been observed in individuals with multiple osteochondromas (PMID: 29529714, 25468659, 19810120). This variant is also known as c.1178+1G>A in the literature. 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 EXT2 are known to be pathogenic (PMID: 19810120). A different variant affecting this nucleotide (c.1079+1G>C) has been determined to be pathogenic (PMID: 11170095). This suggests that this nucleotide is important for normal RNA splicing, and that other variants at this position may also be pathogenic. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 6 of the EXT2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |