Submissions for variant NM_003126.4(SPTA1):c.5572C>G (p.Leu1858Val)

gnomAD frequency: 0.25425  dbSNP: rs3737515

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV000247499	SCV000309430	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000395775	SCV000349279	benign	Hereditary spherocytosis type 3	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000304497	SCV000349280	benign	Elliptocytosis 2	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000361633	SCV000349281	benign	Pyropoikilocytosis, hereditary	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000247499	SCV000605260	likely benign	not specified	2018-05-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001731550	SCV001981896	benign	not provided	2021-06-28	criteria provided, single submitter	clinical testing	Commonly referred to as the AlphaLELY allele when is cis with c.6531-12C>T, a low expression allele that results in partial skipping of exon 46 and expression of hereditary elliptocytosis when in trans with a pathogenic SPTA1 variant (Wilmotte et al., 1999); Observed with c.6531-12C>T multiple times with a variant on the opposite allele (in trans) in unrelated patients with hereditary pyropoikilocytosis or hereditary elliptocytosis in the published literature; is reported to result in more severe disease when in trans with a pathogenic variant (Niss et al., 2016; Ma et al., 2018; Aggarwal et al., 2020); This variant is associated with the following publications: (PMID: 32287101, 32581362, 31602632, 10192450)
Genome-Nilou Lab	RCV000361633	SCV002057676	benign	Pyropoikilocytosis, hereditary	2021-07-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000395775	SCV002057677	benign	Hereditary spherocytosis type 3	2021-07-15	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000304497	SCV002057678	benign	Elliptocytosis 2	2021-07-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001731550	SCV002438991	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001731550	SCV002562949	pathogenic	not provided	2021-10-01	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001731550	SCV005262308	likely benign	not provided		criteria provided, single submitter	not provided
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003794	SCV001162238	likely pathogenic	Hemolytic anemia		flagged submission	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000247499	SCV001744507	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000247499	SCV001927422	benign	not specified		no assertion criteria provided	clinical testing