Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department of Genetic, |
RCV000655910 | SCV000777859 | likely pathogenic | Hereditary spherocytosis type 2 | 2018-02-27 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001379964 | SCV001577880 | pathogenic | not provided | 2024-07-12 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 23 of the SPTB gene. It does not directly change the encoded amino acid sequence of the SPTB protein. It affects a nucleotide within the consensus splice site. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with spherocytosis (PMID: 29572776, 31807509; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 544813). 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. For these reasons, this variant has been classified as Pathogenic. |
| Mayo Clinic Laboratories, |
RCV001379964 | SCV001714477 | likely pathogenic | not provided | 2019-12-18 | criteria provided, single submitter | clinical testing | PS4_moderate, PM2, PP3, PP5 |
| Revvity Omics, |
RCV001379964 | SCV003815410 | likely pathogenic | not provided | 2022-09-24 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001379964 | SCV005877207 | likely pathogenic | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing | The SPTB c.4973+5G>A variant (rs1555367789) is reported in the literature in three individuals affected with hereditary spherocytosis (Mansour-Hendili 2020, Wang 2018, Xue 2019), including once as a de novo mutation. This variant is also reported in ClinVar (Variation ID: 544813). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a weakly conserved nucleotide, but computational analyses (Alamut Visual Plus v.1.5.1) predict that this variant may impact splicing by weakening the nearby canonical donor splice site. Based on available information, this variant is considered to be likely pathogenic. References: Mansour-Hendili L et al. Exome sequencing for diagnosis of congenital hemolytic anemia. Orphanet J Rare Dis. 2020 Jul 8. PMID: 32641076. Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776. Xue J et al. Clinical utility of targeted gene enrichment and sequencing technique in the diagnosis of adult hereditary spherocytosis. Ann Transl Med. 2019 Oct. PMID: 31807509. |