Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001949338 | SCV002237790 | pathogenic | Familial melanoma | 2021-09-14 | criteria provided, single submitter | clinical testing | The CDKN2A gene encodes two different proteins, p16INK4a and p14ARF, which are translated from alternative transcripts that have different open reading frames. This variant is a gross deletion of the genomic region encompassing exons 1 and 2 of the CDKN2A (p16INK4a) transcript, which includes the initiator codon, and exon 2 of the CDKN2A (p14ARF) transcript. The 5' end of this event is unknown, but is likely confined to the region between exon 1 of p16INK4a and exon 1 of p14ARF, as a copy number variation was not detected in exon 1 of the CDKN2A (p14ARF) transcript. This is expected to result in absent or disrupted p16INK4a and p14ARF protein products. Loss-of-function variants in CDKN2A are known to be pathogenic (PMID: 15146471, 16905682). A similar copy number variant has been observed in individual(s) with familial melanoma (PMID: 18612309, 22841127). For these reasons, this variant has been classified as Pathogenic. While the evidence indicates that this variant confers risk of developing CDKN2A (p16INK4a)-associated conditions, its association with risk for developing CDKN2A (p14ARF)-associated conditions is still unclear. |