Submissions for variant NM_017780.4(CHD7):c.657C>T (p.Gly219=)

gnomAD frequency: 0.00881  dbSNP: rs113483301

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081851	SCV000113786	benign	not specified	2014-10-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000081851	SCV000312993	likely benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000395599	SCV000474375	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000145687	SCV000562425	benign	CHARGE syndrome	2025-02-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000590132	SCV000699438	benign	not provided	2016-06-27	criteria provided, single submitter	clinical testing	Variant summary: The CHD7 c.657C>T (p.Gly219Gly) variant involves the alteration of a conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant and 4/5 slice site tools predict the variant not to have an impact on normal splicing. This variant was found in 285/120590 control chromosomes (9 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.027295 (267/9782). This frequency is about 21836 times the estimated maximal expected allele frequency of a pathogenic CHD7 variant (0.0000013), highly suggesting this is a benign polymorphism found primarily in the populations of African origin. The variant was identified in at least one African American atypical CHARGE syndrome case reported in the literature without providing evidence of causality (ie. functional studies on the variant or co-segregation with disease). A clinical diagnostic laboratory and a publication classify the variant as benign (Bartels_GTMB_2010). Taken together and based on the synonymous nature of the variant and its high allele frequency in the general population, this variant was classified as Benign.
Ambry Genetics	RCV002311672	SCV000847331	benign	Inborn genetic diseases	2016-07-01	criteria provided, single submitter	clinical testing	This alteration is classified as 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	RCV000081851	SCV000967052	benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.Gly219Gly in exon 2 of CHD7: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 2.73% (267/9782) of A frican chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadi nstitute.org; dbSNP rs113483301).
GeneDx	RCV000590132	SCV001900547	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000145687	SCV000192820	benign	CHARGE syndrome	2013-02-08	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000081851	SCV001920946	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081851	SCV001957886	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000081851	SCV001963891	benign	not specified		no assertion criteria provided	clinical testing