ClinVar Miner

Submissions for variant NM_021969.3(NR0B2):c.157_166del (p.His53fs)

dbSNP: rs540387719
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002249486 SCV002517775 benign not specified 2022-05-04 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002535765 SCV003265482 uncertain significance not provided 2021-02-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.His53Alafs*50) in the NR0B2 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in NR0B2 cause disease. This variant is present in population databases (rs540387719, ExAC 0.7%). This variant has been observed in individual(s) with mild obesity as well as non-obese controls (PMID: 11136233, 20233523). ClinVar contains an entry for this variant (Variation ID: 636299). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity RCV003133593 SCV003814140 uncertain significance Inherited obesity 2021-06-10 criteria provided, single submitter clinical testing
Colorectal Cancer Research Lab, Singapore General Hospital RCV000859985 SCV000926957 likely pathogenic APC-mutation negative familial colorectal cancer 2019-05-31 no assertion criteria provided research
PreventionGenetics, part of Exact Sciences RCV003965583 SCV004779804 uncertain significance NR0B2-related disorder 2023-11-10 no assertion criteria provided clinical testing The NR0B2 c.157_166del10 variant is predicted to result in a frameshift and premature protein termination (p.His53Alafs*50). This variant was reported in an individual with obesity (Table 1, Nishigori et al. 2001. PubMed ID: 11136233; Table 2, Yang et al. 2010. PubMed ID: 20233523). This variant has also been reported in a colorectal cancer cohort study (Lam et al. 2020. PubMed ID: 33094510). Experimental studies suggest this variant impacts protein function (Fig 2, Nishigori et al. 2001. PubMed ID: 11136233). This variant is reported in 0.65% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/1-27240265-CAGGTGCGATG-C), which is higher than expected for a primary disease causing variant. Loss of function is not an established mechanism of NR0B2-associated disease. Although we suspect that this variant may be benign, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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