Submissions for variant NM_000089.4(COL1A2):c.2673G>A (p.Val891=)

dbSNP: rs1114167364

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001856923	SCV002267628	uncertain significance	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2020-11-06	criteria provided, single submitter	clinical testing	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. Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has been observed in individual(s) with clinical features of autosomal dominant osteogenesis imperfecta (Invitae). ClinVar contains an entry for this variant (Variation ID: 427739). This variant is not present in population databases (ExAC no frequency). This sequence change affects codon 891 of the COL1A2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the COL1A2 protein. This variant also falls at the last nucleotide of exon 41, which is part of the consensus splice site for this exon.
Institute of Human Genetics, Cologne University	RCV000490639	SCV000538199	likely pathogenic	Osteogenesis imperfecta, perinatal lethal		no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000490639	SCV004099305	likely pathogenic	Osteogenesis imperfecta, perinatal lethal	2023-10-30	no assertion criteria provided	clinical testing