Submissions for variant NM_000037.4(ANK1):c.2803C>T (p.Arg935Ter)

dbSNP: rs2150597061

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001802420	SCV002048031	pathogenic	Hereditary spherocytosis type 1	2023-03-29	criteria provided, single submitter	clinical testing	The ANK1 c.2803C>T; p.Arg935Ter variant is reported in the literature in multiple individuals with spherocytosis or hemolytic anemia (Choi 2019, Del Orbe Barreto 2016, Gao 2018, Muramatsu 2017, Tole 2020, Wang 2018). This variant is also reported in ClinVar (Variation ID: 1330761). This variant is absent from the Genome Aggregation Database, indicating it is not a common polymorphism. This variant induces an early termination codon and is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. REFERENCES Choi HS et al. Molecular diagnosis of hereditary spherocytosis by multi-gene target sequencing in Korea: matching with osmotic fragility test and presence of spherocyte. Orphanet J Rare Dis. 2019 May 23. PMID: 31122244 Del Orbe Barreto R et al. Detection of new pathogenic mutations in patients with congenital haemolytic anaemia using next-generation sequencing. Int J Lab Hematol. 2016 Dec. PMID: 27427187 Gao Y et al. Diagnosis of Hereditary Spherocytosis and Secondary Hemochromatosis in a Patient with Jaundice. Acta Haematol. 2018 PMID: 29597199 Muramatsu H et al. Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Genet Med. 2017 Jul. PMID: 28102861 Tole S et al. Genotype-phenotype correlation in children with hereditary spherocytosis. Br J Haematol. 2020 Nov. PMID: 32436265 Wang R et al. Exome sequencing confirms molecular diagnoses in 38 Chinese families with hereditary spherocytosis. Sci China Life Sci. 2018 Aug. PMID: 29572776
Labcorp Genetics (formerly Invitae), Labcorp	RCV001869471	SCV002247483	pathogenic	not provided	2024-01-24	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg935*) in the ANK1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ANK1 are known to be pathogenic (PMID: 8640229). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hereditary spherocytosis (PMID: 27427187, 29597199, 31122244, 32436265, 33074480, 33620149). This variant is also known as p.Arg976*. ClinVar contains an entry for this variant (Variation ID: 1330761). For these reasons, this variant has been classified as Pathogenic.
Jiangsu Institute of Hematology, the First Affiliated Hospital of Soochow University	RCV001802420	SCV002499992	pathogenic	Hereditary spherocytosis type 1	2022-03-01	criteria provided, single submitter	research
Revvity Omics, Revvity	RCV001802420	SCV003817329	pathogenic	Hereditary spherocytosis type 1	2023-04-25	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV001869471	SCV004227601	pathogenic	not provided	2024-09-19	criteria provided, single submitter	clinical testing