ClinVar Miner

Submissions for variant NM_001159773.2(CANT1):c.836-9G>A

gnomAD frequency: 0.00001  dbSNP: rs538543007
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000178383 SCV000230452 likely pathogenic not provided 2014-10-22 criteria provided, single submitter clinical testing
3billion RCV001775089 SCV002011914 likely pathogenic Desbuquois dysplasia 1 2021-10-02 criteria provided, single submitter clinical testing It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000012, PM2). The variant was observed in trans with a pathogenic variant [NM_001159772.1:c.643G>A (p.Glu215Lys)] as compound heterozygous (3billion dataset, PM3). In silico tools predict the variant to alter splicing and produce an abnormal transcript (SpliceAI: 0.96). Patient's phenotype is considered compatible with Desbuquois dysplasia 1 (3billion dataset, PP4). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline
Labcorp Genetics (formerly Invitae), Labcorp RCV000178383 SCV002194705 pathogenic not provided 2024-01-25 criteria provided, single submitter clinical testing This sequence change falls in intron 3 of the CANT1 gene. It does not directly change the encoded amino acid sequence of the CANT1 protein. RNA analysis indicates that this variant induces altered splicing and likely disrupts the C-terminus of the protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has been observed in individual(s) with clinical features of Desbuquois dysplasia (PMID: 21037275; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as IVS2-9G>A. ClinVar contains an entry for this variant (Variation ID: 197369). Studies have shown that this variant results in alternative splicing and inclusion of intronic sequence (c.835_836insTTCCCAG) and introduces a new termination codon (PMID: 21037275). However the mRNA is not expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.

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