ClinVar Miner

Submissions for variant NM_022132.5(MCCC2):c.1574+1G>A

gnomAD frequency: 0.00002  dbSNP: rs730880265
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000002005 SCV001199839 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2023-10-08 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 16 of the MCCC2 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is present in population databases (rs730880265, gnomAD 0.003%). Disruption of this splice site has been observed in individual(s) with 3-methylcrotonyl-CoA carboxylase deficiency (PMID: 16010683). ClinVar contains an entry for this variant (Variation ID: 1928). Variants that disrupt 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. This variant disrupts a region of the MCCC2 protein in which other variant(s) (p.Gly559Asp) have been determined to be pathogenic (PMID: 27033733; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000002005 SCV000022163 pathogenic 3-methylcrotonyl-CoA carboxylase 2 deficiency 2005-01-01 no assertion criteria provided literature only

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