ClinVar Miner

Submissions for variant NM_017780.4(CHD7):c.7579A>C (p.Met2527Leu) (rs192129249)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000145693 SCV000192801 likely benign not specified 2013-02-08 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000145693 SCV000202473 benign not specified 2014-03-03 criteria provided, single submitter clinical testing
Invitae RCV000203938 SCV000259930 benign CHARGE association 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000145693 SCV000312999 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000677330 SCV000474506 benign Hypogonadotropic hypogonadism 5 with or without anosmia 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000203938 SCV000474507 likely benign CHARGE association 2016-06-14 criteria provided, single submitter clinical testing
GeneDx RCV000145693 SCV000512584 likely benign not specified 2016-06-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
SIB Swiss Institute of Bioinformatics RCV000677330 SCV000803567 benign Hypogonadotropic hypogonadism 5 with or without anosmia 2018-05-31 criteria provided, single submitter curation This variant is interpreted as a Benign, for Hypogonadotropic hypogonadism 5 with or without anosmia, in Autosomal Dominant manner. The following ACMG Tag(s) were applied: BS4 => Lack of segregation in affected members of a family (PMID:25077900). BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
Ambry Genetics RCV000716204 SCV000847041 likely benign History of neurodevelopmental disorder 2017-06-14 criteria provided, single submitter clinical testing Does not segregate with disease in family study (genes with incomplete penetrance);In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000145693 SCV000966271 benign not specified 2018-12-04 criteria provided, single submitter clinical testing The p.Met2527Leu variant in CHD7 is classified as benign because it has been ide ntified in 0.36% (407/113196) of European chromosomes, including 1 homozygous in dividual, by gnomAD (http://gnomad.broadinstitute.org) and due to a lack of cons ervation across species, including mammals. Of note, four mammals have a leucine (Leu) at this position despite high nearby amino acid conservation. In addition , computational prediction tools do not suggest a high likelihood of impact to t he protein. Finally, although this variant has been reported in individuals with CHARGE syndrome, it was also identified in their unaffected parents (Bartels 20 10, Marcos 2014). ACMG/AMP Criteria applied: BA1, BP4_Strong, BS4.
Mendelics RCV000203938 SCV001137636 likely benign CHARGE association 2019-05-28 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000145693 SCV001159208 likely benign not specified 2019-06-22 criteria provided, single submitter clinical testing

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