Submissions for variant NM_000393.5(COL5A2):c.403-3T>C

gnomAD frequency: 0.00010  dbSNP: rs369733690

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000251413	SCV000304007	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000290624	SCV000425668	uncertain significance	Ehlers-Danlos syndrome type 7A	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV002230200	SCV000547870	uncertain significance	Ehlers-Danlos syndrome, classic type, 1	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change falls in intron 5 of the COL5A2 gene. It does not directly change the encoded amino acid sequence of the COL5A2 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs369733690, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL5A2-related conditions. ClinVar contains an entry for this variant (Variation ID: 256003). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Center for Human Genetics Tuebingen	RCV000487930	SCV000575292	likely benign	not provided	2021-06-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313976	SCV000738732	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2024-01-29	criteria provided, single submitter	clinical testing	The c.403-3T>C intronic variant results from a T to C substitution 3 nucleotides upstream from coding exon 6 in the COL5A2 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Based on the available evidence, the clinical significance of this alteration remains unclear.
GeneDx	RCV000487930	SCV000968877	likely benign	not provided	2020-07-10	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002277609	SCV002565838	likely benign	Ehlers-Danlos syndrome	2020-11-17	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV003144177	SCV003833747	uncertain significance	Ehlers-Danlos syndrome, classic type, 2	2020-10-29	criteria provided, single submitter	clinical testing