Submissions for variant NM_017780.4(CHD7):c.7551A>G (p.Lys2517=)

gnomAD frequency: 0.00048  dbSNP: rs202020722

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000333331	SCV000474505	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000275903	SCV000631276	benign	CHARGE syndrome	2025-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV001706605	SCV000732782	likely benign	not provided	2021-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002314088	SCV000849042	likely benign	Inborn genetic diseases	2017-01-17	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000602581	SCV000966392	likely benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.Lys2517Lys in exon 34 of CHD7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue and is not located w ithin the splice consensus sequence. It has been identified in 0.36% (24/6614) o f Finnish chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs202020722).
CeGaT Center for Human Genetics Tuebingen	RCV001706605	SCV004155876	likely benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	CHD7: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003932505	SCV004750896	likely benign	CHD7-related disorder	2022-02-08	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).