ClinVar Miner

Submissions for variant NM_000037.4(ANK1):c.1801-17G>A

dbSNP: rs786205243
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Total submissions: 7
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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 RCV000655898 SCV000777846 pathogenic Hereditary spherocytosis type 1 2018-02-27 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001091597 SCV001247729 likely pathogenic not provided 2019-09-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001091597 SCV001714273 likely pathogenic not provided 2024-09-20 criteria provided, single submitter clinical testing PM2, PS3, PS4_moderate
Revvity Omics, Revvity RCV000655898 SCV003828354 likely pathogenic Hereditary spherocytosis type 1 2023-12-19 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000655898 SCV004563382 likely pathogenic Hereditary spherocytosis type 1 2023-09-29 criteria provided, single submitter clinical testing The ANK1 c.1801-17G>A variant (rs786205243) has been reported in multiple individuals from families affected with hereditary spherocytosis (HS) (Duru 1992, Edelman 2007, Kang 2020). This variant is also reported in ClinVar (Variation ID: 513). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This is an intronic variant in a moderately conserved nucleotide, and computational analyses (Alamut Visual Plus v.1.5.1) predict that this variant does not alter splicing in a significant way. However, in-vitro functional assays suggest altered splicing by creating a novel cryptic acceptor splice site. Based on available information, this variant is considered to be likely pathogenic. REFERENCES Duru F et al. Homozygosity for dominant form of hereditary spherocytosis. Br J Haematol. 1992 Nov. PMID: 1486040 Edelman EJ et al. A complex splicing defect associated with homozygous ankyrin-deficient hereditary spherocytosis. Blood. 2007 Jun 15. PMID: 17327413 Kang LL et al. Gilbert's syndrome coexisting with hereditary spherocytosis might not be rare: Six case reports. World J Clin Cases. 2020 May 26. PMID: 32518793
Labcorp Genetics (formerly Invitae), Labcorp RCV001091597 SCV005835376 pathogenic not provided 2024-12-18 criteria provided, single submitter clinical testing This sequence change falls in intron 16 of the ANK1 gene. It does not directly change the encoded amino acid sequence of the ANK1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with hereditary spherocytosis (PMID: 17327413, 32518793, 32641076; internal data). ClinVar contains an entry for this variant (Variation ID: 513). Studies have shown that this variant is associated with altered splicing resulting in multiple RNA products (PMID: 17327413). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000000542 SCV000020691 pathogenic SPHEROCYTOSIS, TYPE 1, AUTOSOMAL RECESSIVE 2007-06-15 no assertion criteria provided literature only

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