Submissions for variant NM_000037.4(ANK1):c.2830G>A (p.Ala944Thr)

gnomAD frequency: 0.00170  dbSNP: rs35797405

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000897766	SCV001041927	likely benign	not provided	2023-04-06	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001161489	SCV001323371	likely benign	Hereditary spherocytosis type 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV001161490	SCV001323372	uncertain significance	Spherocytosis	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Mayo Clinic Laboratories, Mayo Clinic	RCV000897766	SCV001715992	uncertain significance	not provided	2022-06-28	criteria provided, single submitter	clinical testing
GeneDx	RCV000897766	SCV001988970	uncertain significance	not provided	2020-01-03	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Identified by exome sequencing in the heterozygous state in a male child with severe transfusion dependent anemia who was homozygous for a disease-causing frameshift variant in the EPB41 gene (Lacy et al., 2016); This variant is associated with the following publications: (PMID: 27551681)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001161489	SCV002506010	uncertain significance	Hereditary spherocytosis type 1	2022-02-03	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003940804	SCV004755374	likely benign	ANK1-related condition	2019-10-02	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).