Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV000021237 | SCV000603150 | benign | X-linked Alport syndrome | 2018-12-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001588820 | SCV001827038 | likely benign | not provided | 2020-02-26 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003155037 | SCV003844887 | benign | not specified | 2023-02-17 | criteria provided, single submitter | clinical testing | Variant summary: COL4A5 c.1033-15delT alters a non-conserved nucleotide within a poly-T region located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0068 in 133794 control chromosomes in the gnomAD database, including 5 homozygotes. The observed variant frequency is approximately 1.5-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL4A5 causing Alport Syndrome 1, X-Linked Recessive phenotype (0.0046), strongly suggesting that the variant is benign. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |