Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001410999 | SCV001613055 | likely benign | not provided | 2023-07-28 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003120602 | SCV003800795 | uncertain significance | not specified | 2023-01-25 | criteria provided, single submitter | clinical testing | Variant summary: HBB c.316-42delC is located at a position not widely known to affect splicing. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2e-05 in 250284 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.316-42delC has been reported in the literature in a healthy individual in trans with a pathogenic HBB variant (c.316-106C>G; fully concordant pathogenic classifications in ClinVar and scored as pathogenic in internal database); the individual with the variant of interest was comprehensively phenotyped and found to have "normal hematological and electrophoretic features" (Vinciguerra_2017). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |