Submissions for variant NM_017780.4(CHD7):c.7590A>G (p.Lys2530=)

gnomAD frequency: 0.00476  dbSNP: rs61742801

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000145694	SCV000192802	uncertain significance	CHARGE syndrome	2013-02-08	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000249926	SCV000313000	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000249926	SCV000512585	benign	not specified	2016-04-25	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000145694	SCV000562416	benign	CHARGE syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002312635	SCV000847347	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	RCV000249926	SCV001365642	benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.Lys2530Lys in exon 34 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 1.54% (143/9280) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs61742801).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000249926	SCV004813150	benign	not specified	2024-02-27	criteria provided, single submitter	clinical testing	Variant summary: CHD7 c.7590A>G alters a conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0012 in 200010 control chromosomes, predominantly at a frequency of 0.015 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 300 fold of the estimated maximal expected allele frequency for a pathogenic variant in CHD7 causing CHARGE Syndrome phenotype (4.4e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. ClinVar contains an entry for this variant (Variation ID: 158318). Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000249926	SCV001743370	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000249926	SCV001923401	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000249926	SCV001954938	benign	not specified		no assertion criteria provided	clinical testing