Submissions for variant NM_002775.5(HTRA1):c.972+1G>A

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002667870	SCV002984027	likely pathogenic	not provided	2022-07-19	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 4 of the HTRA1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HTRA1 are known to be pathogenic (PMID: 19387015, 29895533). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with HTRA1-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx	RCV002667870	SCV004021585	likely pathogenic	not provided	2023-07-21	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in an in-frame loss of the adjacent exon in a gene for which loss of function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV004066843	SCV005016564	pathogenic	Age related macular degeneration 7	2024-03-14	criteria provided, single submitter	clinical testing