Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001267360 | SCV001445541 | likely pathogenic | Inborn genetic diseases | 2020-05-06 | criteria provided, single submitter | clinical testing | The alteration results in a premature stop codon: The c.794delT (p.L265Rfs*15) alteration, located in coding exon 4 of the BCL11A gene, results from a deletion one nucleotide at position 794, causing a translational frameshift with a predicted alternate stop codon after 15 amino acids. Frameshifts are typically deleterious in nature; however, this frameshift occurs at the 3' terminus of BCL11A, is not expected to trigger nonsense-mediated mRNA decay, and a truncated mutant protein could still be expressed (Maquat, 2004). This alteration impacts the last amino 511 acids of the protein. The exact functional effect of the altered amino acids is unknown; however, premature stop codons are typically deleterious in nature and a significant portion of the protein is affected (Ambry internal data). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the BCL11A c.794delT alteration was not observed, with coverage at this position. Based on the available evidence, this alteration is classified as likely pathogenic. |