Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586836 | SCV000697112 | uncertain significance | not provided | 2017-04-06 | criteria provided, single submitter | clinical testing | Variant summary: The HBB c.316-138G>A involves alteration of a non-conserved nucleotide in intron 2. Mutation taster predicts benign outcome of this variant and 5/5 splice prediction tools also predict no effect on splicing. However, these predictions have not been confirmed by functional studies. Intron 2 in HBB gene is relatively small (consiting of 850 nucleotides) and is known to be of clinical importance as deep intronic variants, such as c.316-106C>G, c.316-146T>G and c.316-197C>T), are known to be pathogenic/likely pathogenic as well. Therefore at this time, role of the variant of interest in splicing cannot be ruled out with certainty. This variant position has not been covered in ExAC, NHLBI ESP and 1000 Genomes but is reported at an allele frequency of 0.00003229 (1/30968 chromosomes) in gnomAD database (a new database that combines data from ExAC and additional whole genome sequences, however, it has yet to be validated by the LCA VSG, as of yet). The variant of interest has not, to our knowledge, been reported via publications, clinical diagnostic laboratories, or reputable databases. Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)." |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000586836 | SCV001134224 | likely benign | not provided | 2022-09-16 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000586836 | SCV001632462 | likely benign | not provided | 2023-07-19 | criteria provided, single submitter | clinical testing |