Submissions for variant NM_017780.4(CHD7):c.6822T>C (p.Ala2274=)

gnomAD frequency: 0.00021  dbSNP: rs61743849

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724311	SCV000229558	uncertain significance	not provided	2014-12-30	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000177656	SCV000594100	uncertain significance	not specified	2016-07-22	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000177656	SCV000919209	benign	not specified	2017-09-25	criteria provided, single submitter	clinical testing	Variant summary: The CHD7 c.6822T>C (p.Ala2274Ala) 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. 5/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE site of SC35. However, these predictions have yet to be confirmed by functional studies. This variant was found in 42/119700 control chromosomes at a frequency of 0.0003509, which is approximately 281 times the estimated maximal expected allele frequency of a pathogenic CHD7 variant (0.0000013), suggesting this variant is likely a benign polymorphism. Although multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, this variant is classified as benign based on its frequency in controls.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000177656	SCV000967183	likely benign	not specified	2017-08-23	criteria provided, single submitter	clinical testing	p.Ala2274Ala in exon 32 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 0.10% (12/11440) of Latino chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.bro adinstitute.org; dbSNP rs61743849).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082670	SCV001000762	benign	CHARGE syndrome	2024-01-17	criteria provided, single submitter	clinical testing
GeneDx	RCV000724311	SCV001946041	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002362907	SCV002665232	likely benign	Inborn genetic diseases	2017-12-29	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.
CeGaT Center for Human Genetics Tuebingen	RCV000724311	SCV004155870	likely benign	not provided	2023-05-01	criteria provided, single submitter	clinical testing	CHD7: BP4, BP7, BS1
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000724311	SCV001978268	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724311	SCV001980119	likely benign	not provided		no assertion criteria provided	clinical testing