ClinVar Miner

Submissions for variant NM_001024688.2(NBN):c.-141_-140del (rs767454740)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410370 SCV000486614 likely pathogenic Microcephaly, normal intelligence and immunodeficiency 2016-07-07 criteria provided, single submitter clinical testing
Invitae RCV000410370 SCV000553052 pathogenic Microcephaly, normal intelligence and immunodeficiency 2019-11-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Ser53Cysfs*9) in the NBN gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs767454740, ExAC 0.001%). This variant has been observed in an individual affected with hereditary breast and/or ovarian cancer (PMID: 24549055). ClinVar contains an entry for this variant (Variation ID: 371121). Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000484600 SCV000568560 likely pathogenic not provided 2018-07-23 criteria provided, single submitter clinical testing This deletion of two nucleotides in NBN is denoted c.156_157delTT at the cDNA level and p.Ser53CysfsX9 (S53CfsX9) at the protein level. The normal sequence, with the bases that are deleted in brackets, is ACTT[delTT]CTGT. The deletion causes a frameshift which changes a Serine to a Cysteine at codon 53, and creates a premature stop codon at position 9 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. NBN c.156_157delTT has been observed in at least one individual with a personal and/or family history of breast and/or ovarian cancer (Castéra 2014). Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Genetic Services Laboratory,University of Chicago RCV000502852 SCV000595917 likely pathogenic Acute lymphoid leukemia 2016-09-12 criteria provided, single submitter clinical testing
Color RCV000584632 SCV000690667 pathogenic Hereditary cancer-predisposing syndrome 2020-01-15 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000587195 SCV000697948 likely pathogenic Hereditary breast and ovarian cancer syndrome 2016-04-11 criteria provided, single submitter clinical testing Variant summary: The variant of interest causes a frameshift mutation resulting in a predicted truncated NBN protein, a mechanism for disease. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 1/121384, which does not exceed the predicted maximum expected allele frequency for a pathogenic NBN variant of 1/8000 for HBOC. The variant of interest has been reported in an affected individual via a publication that consisted of a cohort of HBOC individuals. The variant of interest has not been reported in clinical laboratories or databases. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as Likely Pathogenic.
Mendelics RCV000410370 SCV000838320 pathogenic Microcephaly, normal intelligence and immunodeficiency 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000584632 SCV001172585 pathogenic Hereditary cancer-predisposing syndrome 2018-12-29 criteria provided, single submitter clinical testing Alterations resulting in premature truncation (e.g.reading frame shift, nonsense);Rarity in general population databases (dbsnp, esp, 1000 genomes)

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