ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.3472+1G>A

dbSNP: rs1554123136
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000537065 SCV000630219 likely pathogenic Congenital contractural arachnodactyly 2017-09-28 criteria provided, single submitter clinical testing 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. This variant is expected to disrupt the splicing of exon 26 which contains a EGF-like domain. Variants predicted to disrupt the splicing of exons containing EGF-like domains are significantly enriched in individuals with congenital contractural arachnodacty and are considered likely pathogenic for the condition (PMID: 11754102, 17345643). 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 is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 26 of the FBN2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.
PreventionGenetics, part of Exact Sciences RCV003409774 SCV004111442 likely pathogenic FBN2-related condition 2023-08-01 criteria provided, single submitter clinical testing The FBN2 c.3472+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature. Other nucleotide substitutions impacting the same canonical splice donor site have been reported in individuals affected with FBN2-related disease (Gupta et al. 2002. PubMed ID: 11754102; Sun et al. 2022. PubMed ID: 35360850). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Variants that disrupt the consensus splice donor site in FBN2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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