Submissions for variant NM_032043.2(BRIP1):c.2258A>G (p.Asp753Gly) (rs745578572)

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Total submissions: 5

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000164317	SCV000214948	uncertain significance	Hereditary cancer-predisposing syndrome	2018-04-17	criteria provided, single submitter	clinical testing	Insufficient or conflicting evidence
Invitae	RCV000234088	SCV000291008	uncertain significance	Familial cancer of breast; Fanconi anemia, complementation group J	2019-10-30	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid with glycine at codon 753 of the BRIP1 protein (p.Asp753Gly). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs745578572, ExAC 0.03%) but has not been reported in the literature in individuals with a BRIP1-related disease. ClinVar contains an entry for this variant (Variation ID: 184968). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Counsyl	RCV000662914	SCV000785853	uncertain significance	Fanconi anemia, complementation group J; Neoplasm of ovary	2017-12-27	criteria provided, single submitter	clinical testing
Color	RCV000164317	SCV000912105	uncertain significance	Hereditary cancer-predisposing syndrome	2019-10-08	criteria provided, single submitter	clinical testing
Leiden Open Variation Database	RCV001194773	SCV001364557	uncertain significance	not provided	2019-08-13	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Yukihide Momozawa.

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