ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.3164G>A (p.Ser1055Asn) (rs786202234)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000164950 SCV000215641 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Other strong data supporting benign classification,Rarity in general population databases (dbsnp, esp, 1000 genomes),Last nucleotide of exon,Conflicting evidence
Invitae RCV000164950 SCV000259244 uncertain significance Hereditary cancer-predisposing syndrome 2015-07-02 criteria provided, single submitter clinical testing This sequence change replaces serine with asparagine at codon 1055 of the RAD50 protein (p.Ser1055Asn). The serine residue is weakly conserved and there is a small physicochemical difference between serine and asparagine. It also falls at the last base of exon 20 of the RAD50 mRNA. This variant has not been published in the literature and is not present in population databases. ClinVar contains an entry for this variant (RCV000164950). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. Furthermore, the asparagine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. Sequence changes at the last base of an exon often results in disrupted mRNA splicing. Algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this intronic variant may alter mRNA splicing, but this prediction has not been confirmed by published transcriptional studies. However, an adenine base is found in multiple mammalian species, suggesting that this variant does not adversely affect mRNA splicing. In summary, this is a novel variant with uncertain impact on splicing and protein function. It has been classified as a Variant of Uncertain Significance.

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