ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1238A>G (p.Asn413Ser) (rs529340553)

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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 RCV000222002 SCV000278532 likely benign Hereditary cancer-predisposing syndrome 2017-06-20 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign),Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene
Color RCV000222002 SCV000903010 likely benign Hereditary cancer-predisposing syndrome 2015-10-20 criteria provided, single submitter clinical testing
GeneDx RCV000589729 SCV000149688 uncertain significance not provided 2018-09-28 criteria provided, single submitter clinical testing This variant is denoted NBN c.1238A>G at the cDNA level, p.Asn413Ser (N413S) at the protein level, and results in the change of an Asparagine to a Serine (AAT>AGT). This variant has not, to our knowledge, been published in the literature as a pathogenic or benign germline variant. NBN Asn413Ser was observed at an allele frequency of 0.12% (37/30,776) in individuals of South Asian ancestry in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether NBN Asn413Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000589729 SCV000697941 uncertain significance not provided 2016-03-01 criteria provided, single submitter clinical testing Variant summary: The c.1838A>G in NBN gene is a missense variant that involves a non-conserved nucleotide and 5/5 in silico tools predict a benign outcome. 4/5 programs in Alamut predict that this variant does not affect normal splicing. ESEfinder predicts that this variant may create a novel site of SRp40. However, these predictions are not confirmed by experimental studies. The variant is present in the broad control population dataset of ExAC, exclusively in South Asian individuals at a frequency 0.12%, including 2 homozygous occurrences. Even though, this frequency does not exceed the maximum expected allele frequency for a pathogenic NBN variant (0.25%) the variant may be an ethnic-specific polymorphism. The variant has not, to our knowledge, been reported in affected individuals via peer-reviewed publications but has been cited by one diagnostic center as VUS. Taking together, the variant was classified as VUS-possibly benign, until additional information becomes available.
Invitae RCV000543630 SCV000634207 likely benign Microcephaly, normal intelligence and immunodeficiency 2018-01-03 criteria provided, single submitter clinical testing

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