ClinVar Miner

Submissions for variant NM_001846.4(COL4A2):c.361-1G>A

dbSNP: rs1880548859
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003049150 SCV003338423 likely pathogenic not provided 2024-10-24 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 6 of the COL4A2 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 COL4A2 are known to be pathogenic (PMID: 22333902, 30315939). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with COL4A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2121413). 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.
3billion RCV005254676 SCV005905559 pathogenic Porencephaly 2 2023-11-29 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. In silico tools predict the variant to alter splicing and produce an abnormal transcript [Splice AI: 0.99 (spliceogenicity >=0.2, non-spliceogenicity <0.1)]. The variant has been reported to be associated with COL4A2 related disorder (ClinVar ID: VCV002121413). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

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