Submissions for variant NM_017780.4(CHD7):c.2185A>G (p.Lys729Glu)

gnomAD frequency: 0.00034  dbSNP: rs41272437

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002312290	SCV000846169	likely benign	Inborn genetic diseases	2018-01-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Eurofins Ntd Llc (ga)	RCV000730848	SCV000858615	uncertain significance	not provided	2017-12-20	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001087413	SCV001001861	likely benign	CHARGE syndrome	2024-01-05	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001164338	SCV001326461	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000730848	SCV001477699	likely benign	not provided	2020-05-03	criteria provided, single submitter	clinical testing
GeneDx	RCV000730848	SCV001946033	benign	not provided	2020-04-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30733481, 33270637)
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV003224382	SCV003919791	likely benign	CHARGE syndrome; Hypogonadotropic hypogonadism 5 with or without anosmia	2022-10-13	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF: 0.08% [29/35346], including 1 homozygote; https://gnomad.broadinstitute.org/variant/8-61707633-A-G?dataset=gnomad_r2_1). It is also present in ClinVar (Variation ID: 587800). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
CeGaT Center for Human Genetics Tuebingen	RCV000730848	SCV005041538	likely benign	not provided	2024-04-01	criteria provided, single submitter	clinical testing	CHD7: BS1
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000730848	SCV001931229	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000730848	SCV001973060	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003945735	SCV004757788	likely benign	CHD7-related disorder	2022-09-01	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).