Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001026394 | SCV001188764 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-12 | criteria provided, single submitter | clinical testing | The c.-73G>A variant is located in the 5' untranslated region (5’ UTR) of the CDKN1B gene. This variant results from a G to A substitution 73 bases upstream from the first translated codon. This alteration was detected in a hemizygous state in an individual with autism, maldescended testes, strabismus and overgrowth. The deleted allele was inherited from his apparently unaffected mother, while the c.-73G>A alteration was found to be de novo. Luciferase reporter assay showed that this alteration decreased transcription, however, it was not decreased more than the CDKN1B c.-79C>T alteration which has been seen with a substantial minor allele frequency in the general population and has only slightly increased odds ratios in association with thyroid cancer, endometrial cancer, neuroblastoma and systemic lupus (Grey W et al. Hum. Mut., 2013 Jun; 34; Capasso M et al. J. Cell. Mol. Med., 2017 Jun; Landa I et al. Endocr. Relat. Cancer, 2010 Jun;17:317-28; Chang BL et al. Cancer Res., 2004 Mar;64:1997-9; Cai H et al. Am. J. Epidemiol., 2011 Jun;173:1263-71; Yang W et al. Am. J. Hum. Genet., 2013 Jan;92:41-51). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Illumina Laboratory Services, |
RCV001112160 | SCV001269787 | uncertain significance | Multiple endocrine neoplasia type 4 | 2017-08-08 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |