Description
This variant is denoted BRCA1 c.4675G>A at the cDNA level. Using alternate nomenclature, this variant has been previously published as BRCA1 4794G>A. Located in last nucleotide of exon 14, multiple splicing models predict that this variant destroys the natural splice donor site for intron 14 and causes abnormal splicing. BRCA1 c.4675G>A has been reported in at least three individuals with ovarian cancer (Wappenschmidt 2012, Janavicius 2014, Tihomirova 2014). In addition, RNA analysis suggested that this variant results in partial loss of the natural splice donor site and activation of a cryptic splice donor site (Wappenschmidt 2012). Although the nucleotide substitution results in the change of a Glutamic Acid to a Lysine at codon 1559, and is called Glu1559Lys in the literature, we are using only the nucleotide nomenclature to refer to the mutation since the defect is mainly due to abnormal splicing rather than a resulting missense pathogenic variant. BRCA1 c.4675G>A was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The nucleotide which is altered, a guanine (G) at base 4675, is conserved across species. Based on the current evidence, we consider this mutation to be a likely pathogenic variant.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | yes | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |