Submissions for variant NM_017780.4(CHD7):c.309G>A (p.Ser103=)

gnomAD frequency: 0.00586  dbSNP: rs115293759

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000081829	SCV000113764	benign	not specified	2013-09-26	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000081829	SCV000312968	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000081829	SCV000512577	benign	not specified	2016-04-22	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.
Invitae	RCV001081291	SCV000562417	benign	CHARGE association	2024-01-30	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586712	SCV000699436	benign	not provided	2016-06-27	criteria provided, single submitter	clinical testing	Variant summary: The CHD7 c.309G>A (p.Ser103Ser) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant, but 5/5 splicing algorithms predict no significant change to normal splicing. This variant was found in 199/119626 control chromosomes (3 homozygotes) at a frequency of 0.0016635, which is approximately 1331 times the estimated maximal expected allele frequency of a pathogenic CHD7 variant (0.0000013), suggesting this variant is likely a benign polymorphism. The variant has been cited in at least one CHARGE syndrome patient in the literature without evidence of causality (Jain_Int J Pediatr Endocrinol_2011). In addition, one clinical diagnostic laboratory classified this variant as benign. Based on the synonymous nature of this variant and the high allele frequency in the general population, this variant was classified as benign.
Ambry Genetics	RCV002311665	SCV000847345	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: 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	RCV000081829	SCV001365640	benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.Ser103Ser in exon 2 of CHD7: This variant is not expected to have clinical significance because it does not alter an amino acid residue, is not located within the splice consensus sequence, and has been identified in 1.89% (183/9668) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs115293759).
Genetic Services Laboratory, University of Chicago	RCV000081829	SCV002071506	benign	not specified	2019-08-28	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002477240	SCV002797453	likely benign	CHARGE association; Hypogonadotropic hypogonadism 5 with or without anosmia	2021-07-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000081829	SCV001917897	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000081829	SCV001953514	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000081829	SCV001976214	benign	not specified		no assertion criteria provided	clinical testing