Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001199923 | SCV001370699 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2020-05-04 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.5152+5G>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a 5 splicing donor site. At least one publication reports that this variant results in skipping of exon 18 (Farber-Katz_2018). The variant was absent in 251212 control chromosomes (gnomAD) but has been reported in the literature in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (Farber-Katz_2018, Song_2014). These data indicate that the variant may be associated with disease. Other nucleotide changes in this position (c.5152+5G>C, c.5152+5G>A) has been reported as pathogenic in ClinVar and HGMD. ClinVar contains an entry for this variant, however no classification is provided (Variation ID: 867708). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Ambry Genetics | RCV002339366 | SCV002641068 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2016-07-06 | criteria provided, single submitter | clinical testing | The c.5152+5G>T intronic variant results from a G to T substitution five nucleotides after coding exon 16 in the BRCA1 gene. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.0004% (greater than 225000 alleles tested) in our clinical cohort. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site. RNA studies have demonstrated this alteration results in abnormal splicing (Ambry internal data). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Brotman Baty Institute, |
RCV001076462 | SCV001242223 | not provided | Breast-ovarian cancer, familial, susceptibility to, 1 | no assertion provided | in vitro |