Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759053 | SCV000888133 | likely pathogenic | not provided | 2021-06-01 | criteria provided, single submitter | clinical testing | The best available variant frequency is uninformative. Found in at least one symptomatic patient. Predicted to have a tolerated effect on the protein. In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. Assessment of experimental evidence suggests this variant results in abnormal protein function. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003234911 | SCV003934596 | uncertain significance | not specified | 2023-05-02 | criteria provided, single submitter | clinical testing | Variant summary: HBA2 c.391G>C (p.Ala131Pro), also known as Hb Sun Prairie results in a non-conservative amino acid change located in the Globin domain (IPR000971) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 248988 control chromosomes. c.391G>C has been reported in the literature as a homozygous genotype in multiple reports of individuals with features of chronic hemolysis some of who tested negative for the common deletions in the HBA genes (example, Harkness_1990, Plaseska_1990, Ho_1996, Sarkar_2005, Passarello_2008, Tamaddon_2009, Bayat_2013, Jain_2021). However some of these reports also describe the presence of this variant in cis with other alterations in the HBA2 gene such as a C > T transition in the 5'-untranslated region (UTR) (Sarkar_2005), or HBA2 26 G > A (Hb Caserta) (Passarello_2008, Tamaddon_2009). Variable extent of genotyping results reported make it challenging to determine the role of this variant in isolation. Therefore, these data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 23402770, 26523940, 2079430, 8811313, 32199931, 18691171, 2079431, 15813858, 19373587). One clinical diagnostic laboratory and the OMIM database have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely pathogenic citing overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant in isolation was classified as VUS-possibly pathogenic. |
| ARUP Laboratories, |
RCV000759053 | SCV004564996 | pathogenic | not provided | 2023-06-08 | criteria provided, single submitter | clinical testing | The Hb Sun Prairie variant (HBA2: c.391G>C; p.Ala131Pro, also known as Ala130Pro when numbered from the mature protein, rs41529844, HbVar ID: 197) is a unstable hemoglobin reported in the literature in heterozygous individuals affected with microcytosis and hypochromia or with no symptoms (See HbVar and references therin). Homozygosity for Hb Sun Prairie is associated with Hb H disease and chronic hemolytic anemia (Hbvar, Farashi 2016, Jain 2021). This variant is also reported in ClinVar (Variation ID: 15640) and is found in the South Asian population with an allele frequency of 0.01% (3/30252 alleles) in the Genome Aggregation Database. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar database: https://globin.bx.psu.edu/hbvar/menu.html Farashi S et al. Point mutations which should not be overlooked in Hb H disease. Expert Rev Hematol. 2016 Jan;9(1):107-13. PMID: 26523940. Jain A et al. Hb Sun Prairie: A rare cause of chronic hemolysis in an Indian patient. Hematol Oncol Stem Cell Ther. 2021 Sep;14(3):257-259. PMID: 32199931. |
| OMIM | RCV000016926 | SCV000037197 | other | HEMOGLOBIN SUN PRAIRIE | 2018-05-21 | no assertion criteria provided | literature only |