Submissions for variant NM_017780.4(CHD7):c.6775G>A (p.Ala2259Thr)

gnomAD frequency: 0.00014  dbSNP: rs200806228

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001705556	SCV000512582	likely benign	not provided	2021-05-28	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 22539353, 22033296, 22461308)
Invitae	RCV000696512	SCV000825075	uncertain significance	CHARGE association	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 2259 of the CHD7 protein (p.Ala2259Thr). This variant is present in population databases (rs200806228, gnomAD 0.03%). This missense change has been observed in individual(s) with CHARGE syndrome (PMID: 22033296, 22461308, 22539353). ClinVar contains an entry for this variant (Variation ID: 377654). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002318379	SCV000850792	likely benign	Inborn genetic diseases	2018-12-07	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
Illumina Laboratory Services, Illumina	RCV001164558	SCV001326691	uncertain significance	Hypogonadotropic hypogonadism 5 with or without anosmia	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CeGaT Center for Human Genetics Tuebingen	RCV001705556	SCV002063196	likely benign	not provided	2021-11-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV001821158	SCV002071514	uncertain significance	not specified	2018-04-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902475	SCV004719424	likely benign	CHD7-related condition	2022-02-16	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).