Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Diagnostic Laboratory, |
RCV000207547 | SCV000262767 | pathogenic | X-linked Alport syndrome | 2016-02-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001384768 | SCV001584414 | pathogenic | not provided | 2020-04-29 | 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 COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with Alport syndrome (PMID: 26934356, 16941480, Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 222057). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 24 of the COL4A5 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Prevention |
RCV003417753 | SCV004109594 | pathogenic | COL4A5-related condition | 2023-05-23 | criteria provided, single submitter | clinical testing | The COL4A5 c.1780-1G>T variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant has been observed to segregate in three female family members with hematuria and/or thin basement membrane nephropathy (Kovács et al 2016. PubMed ID: 26934356). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice acceptor site in COL4A5 are expected to be pathogenic. This variant is interpreted as pathogenic. |