Submissions for variant NM_017780.4(CHD7):c.7879C>T (p.Arg2627Ter)

dbSNP: rs1064793346

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482183	SCV000565877	pathogenic	not provided	2022-07-15	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 26538304, 31019026, 32386258, 33888711, 16155193)
Rady Children's Institute for Genomic Medicine, Rady Children's Hospital San Diego	RCV000853243	SCV000996059	pathogenic	CHARGE syndrome	2017-05-23	criteria provided, single submitter	clinical testing	The c.7879C>T (p.Arg2627Ter) variant is a stop-gained variant that is predicted to result in premature termination of the CHD7 protein. This variant is well described in the literature with at least 12 patients affected by CHARGE that carry this variant (PMID: 22461308).The two most frequent variants reported in CHD7, which include p.Arg2627Ter, result in Arginine transitioning to a stop codon. This amino acid position is highly conserved. Based on the combined evidence of the literature and potential functional effects of stop-gained variants, the p.Arg2627Ter variant is classified as pathogenic for CHARGE syndrome.
CeGaT Center for Human Genetics Tuebingen	RCV000482183	SCV001249589	pathogenic	not provided	2017-08-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000853243	SCV002239430	pathogenic	CHARGE syndrome	2022-06-29	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 418655). This premature translational stop signal has been observed in individual(s) with clinical features of CHARGE syndrome (PMID: 16155193, 26538304, 31019026). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg2627*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity	RCV000482183	SCV003818652	pathogenic	not provided	2023-02-01	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000853243	SCV004014001	pathogenic	CHARGE syndrome	2022-12-16	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
Baylor Genetics	RCV000853243	SCV004041455	pathogenic	CHARGE syndrome	2023-02-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902723	SCV004725740	pathogenic	CHD7-related disorder	2024-01-18	no assertion criteria provided	clinical testing	The CHD7 c.7879C>T variant is predicted to result in premature protein termination (p.Arg2627*). This variant has been reported in individuals with CHARGE syndrome (Janssen et al. 2012. PubMed ID: 22461308; Jongmans et al. 2006. PubMed ID: 16155193; Sohn et al. 2016. PubMed ID: 26538304; Li et al. 2020. PubMed ID: 32386258). This variant has not been reported in a large population database, indicating this variant is rare. Nonsense variants in CHD7 are expected to be pathogenic. This variant is interpreted as pathogenic.