ClinVar Miner

Submissions for variant NM_006363.6(SEC23B):c.2150del (p.Ala717fs)

gnomAD frequency: 0.00001  dbSNP: rs1334741748
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000779342 SCV000915935 uncertain significance Congenital dyserythropoietic anemia, type II 2018-10-22 criteria provided, single submitter clinical testing The SEC23B c.2150delC (p.Ala717ValfsTer8) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Ala717ValfsTer8 variant has been reported in a compound heterozygous state with a second missense variant in a patient with congenital dyserythropoietic anemia (Russo et al. 2010). The p.Ala717ValfsTer8 variant was absent from 120 controls (Russo et al. 2010) and it is not found in the 1000 Genomes Project, the Exome Sequencing Project, the Exome Aggregation Consortium or the Genome Aggregation Database. Due to the potential impact of frameshift variants, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for congenital dyserythropoietic anemia. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001873183 SCV002281645 pathogenic Congenital dyserythropoietic anemia, type II; Cowden syndrome 7 2023-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ala717Valfs*8) in the SEC23B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 51 amino acid(s) of the SEC23B protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with congenital dyserythropoietic anemia type II (PMID: 20941788). ClinVar contains an entry for this variant (Variation ID: 632369). This variant disrupts a region of the SEC23B protein in which other variant(s) (p.Phe754Leufs*5) have been determined to be pathogenic (PMID: 27471141; 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.

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