ClinVar Miner

Submissions for variant NM_000518.5(HBB):c.251G>A (p.Gly84Asp)

dbSNP: rs1803195
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811162 SCV001159534 likely benign not provided 2019-12-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003234909 SCV003934601 uncertain significance not specified 2024-05-13 criteria provided, single submitter clinical testing Variant summary: HBB c.251G>A (p.Gly84Asp) 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 damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251428 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.251G>A has been reported in the literature in compound heterozygous individuals with Thalassemia-trait level hemoglobin parameters (examples: Tatsis_1976, Sawangareetrakul_2002, Fucharoen_2005, Uaprasert_2009). The variant was also reported in heterozygous patients with normal hemoglobin parameters and/or no clinical presentation (Yamada_1977, Colah_2016). Additionally, the variant was reported in a case of atypical Hb H disease who carried Hb Constant Spring and a-thalassemia 1 (SEA deletion), along with c.251G>A (Jetsrisuparb_2002). The patients sister who also carried all three variants had no symptoms of anemia. All the clinical evidence reported indicates the variant is not a major contributor to the patients' phenotype. 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: 27408413, 15938724, 11843288, 30489691, 546674, 20838957, 12144064, 1260137, 19460936, 19440680, 35023007, 893127). ClinVar contains an entry for this variant (Variation ID: 15320). Based on the evidence outlined above, the variant was classified as uncertain significance.
OMIM RCV000016560 SCV000036828 other HEMOGLOBIN PYRGOS 2017-12-12 no assertion criteria provided literature only

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