ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.7595C>T (p.Thr2532Met) (rs201032343)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724539 SCV000229735 uncertain significance not provided 2017-04-19 criteria provided, single submitter clinical testing
GeneDx RCV000724539 SCV000568385 uncertain significance not provided 2017-03-13 criteria provided, single submitter clinical testing The T2532M variant in the CHD7 gene has been reported previously in an individual with isolated gonadotropin-releasing hormone (GnRH) deficiency who did not have clinical features consistent with a diagnosis of CHARGE syndrome; familial segregation analysis of this variant was not performed (Balasubramanian et al., 2014). The T2532M variant is observed in 11/9200 (0.12%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). The T2532M variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret T2532M as a variant of uncertain significance.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000768182 SCV000898603 uncertain significance CHARGE association; Hypogonadotropic hypogonadism 5 with or without anosmia 2017-10-10 criteria provided, single submitter clinical testing CHD7 NM_017780 exon 34 p.Thr2532Met (c.7595C>T): This variant has been reported in the literature in 1 individual with Isolated Gonadotropin-Releasing Horming Deficiency (IGD). Of note, this individual was not reported to have any other features of CHARGE syndrome (Balasubramanian 2014 PMID:25472840). This variant is present in 0.1% (44/23216) of African alleles including 1 homozygote in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs201032343). This variant is present in ClinVar (Variation ID:196916). Evolutionary conservation and computational predictive tools for this variant are unclear. In addition, functional studies have shown a deleterious effect of this variant. However, these studies may not accurately represent in vivo human biological function (Balasubramanian 2014 PMID:25472840). In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Mendelics RCV000988069 SCV001137637 uncertain significance CHARGE association 2019-05-28 criteria provided, single submitter clinical testing

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