Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000985716 | SCV001134189 | likely pathogenic | not provided | 2020-09-30 | criteria provided, single submitter | clinical testing | The c.96-1G>A variant (also known as IVS-I-117G>A) is located in a canonical splice-acceptor site and is predicted to interfere with normal HBA1 mRNA splicing. This variant has been described to be of Asian Indian ancestry, and associated with alpha2 thalassemia and hemolytic anemia (HbVar (http://globin.cse.psu.edu/cgi-bin/hbvar/counter) and ITHANET (http://www.ithanet.eu/)). This variant has been reported as homozygous which was also compound heterozygous for Hb S and a beta+-thal, and as heterozygous with just Hb S alone or together with either -3.7kb deletion or -4.2 kb deletion in multiple affected individuals (PMID: 8251382 (1993)). |
ARUP Laboratories, |
RCV000985716 | SCV001474361 | pathogenic | not provided | 2020-08-03 | criteria provided, single submitter | clinical testing | The HBA1 c.96-1G>A variant (rs34883113), also known as alpha1 IVS-I-117 (G->A), has been reported in multiple individuals affected with alpha thalassemia minor, found in-trans with either an alpha globin deletion or homozygously (Curuk 1993, HbVar database). This variant is found in the South Asian population with an overall allele frequency of 0.10% (21/21318 alleles) in the Genome Aggregation Database. This variant abolishes the canonical splice acceptor site of intron 1, which is likely to disrupt gene function. Based on available information, this variant is considered to be pathogenic. References: Link to HbVar for alpha1 IVS-I-117 (G->A): http://globin.bx.psu.edu/cgi-bin/hbvar/query_vars3?mode=output&display_format=page&i=1067 Curuk M et al. An IVS-I-117 (G-->A) acceptor splice site mutation in the alpha 1-globin gene is a nondeletional alpha-thalassaemia-2 determinant in an Indian population. Br J Haematol. 1993; 85(1):148-52. |
Genetics and Molecular Pathology, |
RCV002466598 | SCV002761437 | pathogenic | alpha Thalassemia | 2020-03-20 | criteria provided, single submitter | clinical testing | PVS1, PS3, PP5 |
Fulgent Genetics, |
RCV002503142 | SCV002816765 | pathogenic | Heinz body anemia; alpha Thalassemia; Hemoglobin H disease; Methemoglobinemia, alpha type; Erythrocytosis, familial, 7 | 2021-07-23 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003918611 | SCV004732505 | pathogenic | HBA1-related condition | 2023-11-16 | criteria provided, single submitter | clinical testing | The HBA1 c.96-1G>A variant is predicted to disrupt the AG splice acceptor site and interfere with normal splicing. This variant (also referred to as IVS-I-117) has been reported as a founder variant in the Indian population and is causative for alpha thalassemia (Curuk. 1993. PubMed ID: 8251382; Scheps. 2012. PubMed ID: 22738642). This variant is also interpreted as likely pathogenic and pathogenic in ClinVar. This variant is interpreted as pathogenic. |