ClinVar Miner

Submissions for variant NM_000519.4(HBD):c.82G>T (p.Ala28Ser)

gnomAD frequency: 0.00158  dbSNP: rs35152987
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000398301 SCV000330244 pathogenic not provided 2023-02-02 criteria provided, single submitter clinical testing Published functional studies demonstrate that this variant may affect RNA splicing by strengthening an upstream cryptic splice donor site (Trifillis et al., 1996); In silico analysis supports that this missense variant does not alter protein structure/function; However, In silico analysis supports a deleterious effect on splicing; This variant is associated with the following publications: (PMID: 12402333, 3401592, 1742490, 9054695, 23215833, 1398286, 25333069, 27884173, 20854114, 26754299, 27461962, 23797957, 30487145, 31980526, 34426522, 31688628, 31589614, 33178177, 10975439, 8900178)
Illumina Laboratory Services, Illumina RCV001107109 SCV001264239 likely benign Fetal hemoglobin quantitative trait locus 1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Revvity Omics, Revvity RCV000398301 SCV004236133 pathogenic not provided 2023-07-20 criteria provided, single submitter clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV003987322 SCV004804765 likely pathogenic Glucocorticoid-remediable aldosteronism 2024-03-17 criteria provided, single submitter research
OMIM RCV000016221 SCV000036489 pathogenic delta Thalassemia 2002-11-01 no assertion criteria provided literature only
OMIM RCV000016222 SCV000036490 other HEMOGLOBIN A(2) YIALOUSA 2017-12-12 no assertion criteria provided literature only
Reproductive Health Research and Development, BGI Genomics RCV000016221 SCV001142416 pathogenic delta Thalassemia 2020-01-06 no assertion criteria provided curation NM_000519.3:c.82G>T in the HBD gene has an allele frequency of 0.008 in Ashkenazi Jewish subpopulation in the gnomAD database. The HBD c.82G>T (p.Ala28Ser) was the most common variant found in the HBD gene in a Iran cohort with thalassemia (PMID: 26754299). In addition, De Angioletti et al. also reported that the Hb A2-Yialousa (g.82G>T) was the most prevalent (42/63 families). Functional studies indicate that A28S may affect RNA splicing by strengthening an upstream cryptic splice donor site (PMID: 1742490). Taken together, we interprete this variant as Pathogenic/Likely pathogenic. ACMG/AMP Criteria applied: PS4; PP4; PS3.

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