ClinVar Miner

Submissions for variant NM_000517.6(HBA2):c.377T>G (p.Leu126Arg) (rs41397847)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000985724 SCV001134197 pathogenic not provided 2019-03-19 criteria provided, single submitter clinical testing The best available variant frequency is uninformative because there are too few occurrences in population data. Statistically enriched in patients compared to controls. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. Moderate co-segregation with disease in affected individuals.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001286161 SCV001472690 pathogenic none provided 2019-11-01 criteria provided, single submitter clinical testing The Hb Plasencia variant (HBA2: c.377T>G; p.Leu126Arg, also known as Leu125Arg when numbered from the mature protein, rs41397847) is reported as a hyperunstable hemoglobin variant found heterozygously in individuals with moderate microcytosis and hypochromia, and homozygously in an individual with moderate anemia, jaundice and splenomegaly (Cunha 2013, Garcon 2010, Martin 2005, see HbVar link). This variant is reported in ClinVar (Variation ID: 15690). It is only observed on two alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The leucine at codon 126 is weakly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Other variants at this codon (Hb West-Einde, Hb Quong Sze) are reported in individuals with mild to moderate anemia, microcytosis and hypochroima (see HbVar links). Based on available information, the Hb Plasencia variant is considered to be pathogenic. REFERENCES Link to HbVar for Hb Plasencia: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=1226&.cgifields=histD Link to HbVar for Hb Quong Sze: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=187&.cgifields=histD Link to HbVar for Hb West-Einde: http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=2592&.cgifields=histD Cunha E et al. Hb Plasencia (a125(H8)Leu?Arg (a2)) is a frequent cause of a+-thalassemia in the Portuguese population. Hemoglobin. 2013;37(2):183-7. Garcon L et al. A dyserythropoietic anemia associated with homozygous Hb Plasencia (a125(H8)Leu?Arg (a2)) (HBA2:c.377T>G), a variant with an unstable a chain. Hemoglobin. 2010;34(6):576-81. Martin G et al. A novel mutation of the alpha2-globin causing alpha(+)-thalassemia: Hb Plasencia (alpha125(H8)Leu--Arg (alpha2). Hemoglobin. 2005;29(2):113-7.
OMIM RCV000016981 SCV000037253 other HEMOGLOBIN PLASENCIA 2016-10-13 no assertion criteria provided literature only

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