ClinVar Miner

Submissions for variant NM_000032.4(ALAS2):c.-258C>G (rs140772352)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000433066 SCV000520987 uncertain significance not specified 2017-06-27 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the ALAS2 gene. The c.-258 C>G variant has previously been reported, as c.-206 C>G, in association with X-linked sideroblastic anemia (XLSA) in an affected mother and son (Bekri et al., 2003). Transfection of the c.-258 C>G variant in K562 human erythroid cells found that it is associated with a 94% decrease in promoter activity compared to wildtype (Bekri et al., 2003). The affected mother was also found to have reduced ALAS2 mRNA expression in erythroid precursors (Bekri et al., 2003). However, this substitution occurs at a position that is not conserved and the 1000 Genomes Project Consortium reports c.-258 C>G was observed in 7/766 (0.9%) alleles from individuals of European background including 2 individuals who were hemizygous for c.-258 C>G, indicating it may be a rare benign variant in this population. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
OMIM RCV000011226 SCV000031453 pathogenic Anemia, sideroblastic, 1 2003-07-15 no assertion criteria provided literature only

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