ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.898-2A>T

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV004788639 SCV005399653 likely pathogenic Ehlers-Danlos syndrome, type 4 2024-10-10 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.5, this variant is classified as Likely Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene. Dominant negative is due to missense variants affecting glycine residues in the Gly-X-Y repeat within the triple helical region, while loss of function is due to null alleles (PMID: 29346445). (I) 0108 - This gene is associated with both recessive and dominant disease. There is currently no genotype-phenotype correlation between autosomal dominant Ehlers-Danlos syndrome (EDS), vascular type (MIM#130050) and autosomal recessive polymicrogyria with or without vascular-type EDS (MIM#618343). (I) 0112 - The condition associated with this gene has incomplete penetrance. This is associated with COL3A1 null variants (PMID: 20301667). (I) 0115 - Variants in this gene are known to have variable expressivity (PMID: 20301667). (I) 0211 - Canonical splice site variant without proven consequence on splicing (no functional evidence available). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (v2, v3 and v4). (SP) 0505 - Abnormal splicing is predicted by in silico tools and affected nucleotide is highly conserved. (SP) 0702 - Other splice variants comparable to the one identified in this case have strong previous evidence for pathogenicity. Variants in this canonical splice region, c.898-2A>G, c.898-1G>A and c.898-1G>C, have multiple likely pathogenic and pathogenic reports (ClinVar, LOVD). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

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