ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.2678-1G>T

dbSNP: rs2524403418
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics, Royal Melbourne Hospital RCV003994654 SCV004812434 likely pathogenic X-linked Alport syndrome 2022-12-23 criteria provided, single submitter clinical testing This sequence change in COL4A5 occurs within the canonical splice donor site (+ 1) of intron 32. It is predicted to cause skipping of biologically relevant-exon 32, resulting in an in-frame deletion (removes amino acids 894-923) that is expected to escape nonsense-mediated decay and remove part of the collagen domain critical for protein function. An alternative change at this position (c.2678-1G>A) demonstrated exon 32 skipping in RNA studies (PMID: 29959198). This variant is absent from the population database gnomAD v2.1 and v3.1. This variant has been reported in at least two probands with a phenotype consistent with Alport syndrome (LOVD, Royal Melbourne Hospital). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as LIKELY PATHOGENIC. Following criteria are met: PVS1_Strong, PS4_Supporting, PM2_Supporting.

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