Submissions for variant NM_017780.4(CHD7):c.8477A>G (p.Asn2826Ser)

dbSNP: rs370129047

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000471269	SCV000562426	benign	CHARGE syndrome	2024-01-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194048	SCV001363294	benign	not specified	2019-03-05	criteria provided, single submitter	clinical testing	Variant summary: The variant, CHD7 c.8477A>G (p.Asn2826Ser) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0009 in 276962 control chromosomes, predominantly at a frequency of 0.008 within the South Asian subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 6400 fold of the estimated maximal expected allele frequency for a pathogenic variant in CHD7 causing Congenital Heart Disease phenotype (1.3e-06), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. The variant, c.8477A>G has been reported in the literature in an individual affected with Tetralogy of Fallot (DAlessandro_2016). However, this report does not provide unequivocal conclusions about association of the variant with Congenital Heart Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. A ClinVar submission from a clinical diagnostic laboratory (evaluation after 2014) cites the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV001672798	SCV001890370	benign	not provided	2019-04-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002446908	SCV002680636	likely benign	Inborn genetic diseases	2018-06-13	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.
Fulgent Genetics, Fulgent Genetics	RCV002489132	SCV002798599	likely benign	CHARGE syndrome; Hypogonadotropic hypogonadism 5 with or without anosmia	2021-11-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001672798	SCV004155885	benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	CHD7: BS1, BS2