ClinVar Miner

Submissions for variant NM_001355436.2(SPTB):c.647G>A (p.Arg216Gln)

dbSNP: rs1555371769
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Department of Genetic, Henri Mondor Hospital, Assistance Publique des Hôpitaux de Paris RCV000655908 SCV000777857 likely pathogenic Hereditary spherocytosis type 2 2018-02-27 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003133483 SCV003817162 likely pathogenic not provided 2023-11-15 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003432719 SCV004116553 likely pathogenic SPTB-related disorder 2023-02-07 criteria provided, single submitter clinical testing The SPTB c.647G>A variant is predicted to result in the amino acid substitution p.Arg216Gln. This variant was reported in an individual with jaundice and a patient with hereditary spherocytosis (Wang et al 2018. PubMed ID: 29572776; Vives-Corrons JL et al 2020. PubMed ID: 33074480). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. The c.647G>A variant also resides at the exon/intron boundary and is predicted to weaken the splice donor site based on available splicing prediction programs (Alamut v.2.11). We have observed the c.647G>A variant at PreventionGenetics in other patients with hereditary spherocytosis. This variant is interpreted as likely pathogenic.
Mayo Clinic Laboratories, Mayo Clinic RCV003133483 SCV004224583 pathogenic not provided 2024-05-28 criteria provided, single submitter clinical testing PP1_strong, PP3, PP5, PM2_moderate, PS4_moderate
Labcorp Genetics (formerly Invitae), Labcorp RCV003133483 SCV004538909 uncertain significance not provided 2022-11-14 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 544811). This missense change has been observed in individual(s) with SPTB related conditions (PMID: 29572776, 33074480). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 216 of the SPTB protein (p.Arg216Gln). This variant also falls at the last nucleotide of exon 5, which is part of the consensus splice site for this exon.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004796261 SCV005416974 likely pathogenic Elliptocytosis 3; Hereditary spherocytosis type 2 criteria provided, single submitter clinical testing PM2_Supporting+PP3_Moderate+PS4_Supporting+PP4+PP1_Strong

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