ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.4750_4751delinsAG (p.Glu1584Arg) (rs1064793066)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486064 SCV000564782 uncertain significance not provided 2014-12-29 criteria provided, single submitter clinical testing This variant is denoted BRCA2 c.4750_4751delGAinsAG at the cDNA level, p.Glu1584Arg (E1584R) at the protein level. The normal sequence, with the bases that are deleted and inserted in brackets, is CATT[delGA][insAG]GATC. This in frame deletion and insertion, also denoted BRCA2 c.4978_4979 delGAinsAG using alternate nomenclature, occurs on the same allele (in cis) and results in the missense change of a Glutamic Acid to a Arginine (GAG>AGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Glu1584Arg 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. Since Glutamic Acid and Arginine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu1584Arg occurs at a position that is moderately conserved among mammals and is not located in a known functional domain (UniProt). In addition, in silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, we consider BRCA2 Glu1584Arg to be a variant of uncertain significance.

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