Submissions for variant NM_000089.4(COL1A2):c.2835+1G>A

dbSNP: rs72659310

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV002231121	SCV000956030	pathogenic	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2023-06-15	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 425653). Disruption of this splice site has been observed in individual(s) with autosomal dominant osteogenesis imperfecta (PMID: 15241796, 25944380, 26177859, 29595812). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 43 of the COL1A2 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 COL1A2 are known to be pathogenic (PMID: 11288717, 15077201).
Neuberg Centre For Genomic Medicine, NCGM	RCV000490660	SCV005042940	pathogenic	Osteogenesis imperfecta with normal sclerae, dominant form		criteria provided, single submitter	clinical testing	The splice donor c.2835+1G>A variant in the COL1A2 gene has been observed in individuals with autosomal dominant osteogenesis imperfecta Lindahl, Katarina et al., 2015. The variant is novel not in any individuals in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The variant is in 43 introns and affects the GT donor splice site downstream of exon 43. Loss of function variants have been previously reported to be disease causing. For these reasons, this variant has been classified as Pathogenic.
Department of Medical Sciences, Uppsala University	RCV000490726	SCV000574654	pathogenic	Osteogenesis imperfecta type I		no assertion criteria provided	clinical testing
Department of Medical Sciences, Uppsala University	RCV000490660	SCV000574655	pathogenic	Osteogenesis imperfecta with normal sclerae, dominant form		no assertion criteria provided	clinical testing
Institute Of Reproduction And Development, Obstetrics and Gynecology Hospital, Fudan University	RCV003155210	SCV003844082	pathogenic	See cases	2021-09-30	no assertion criteria provided	research