NM_017780.4(CHD7):c.4645-1G>A AND CHARGE syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 11, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003602551.2

Allele description [Variation Report for NM_017780.4(CHD7):c.4645-1G>A]

NM_017780.4(CHD7):c.4645-1G>A

Gene:

CHD7:chromodomain helicase DNA binding protein 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q12.2

Genomic location:

Preferred name:

NM_017780.4(CHD7):c.4645-1G>A

HGVS:

NC_000008.11:g.60841846G>A
NG_007009.1:g.168067G>A
NM_001316690.1:c.1717-20383G>A
NM_017780.4:c.4645-1G>AMANE SELECT
LRG_176:g.168067G>A
NC_000008.10:g.61754405G>A

Molecular consequence:

NM_001316690.1:c.1717-20383G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_017780.4:c.4645-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: CHARGE syndrome (CHARGE)
Synonyms:: CHARGE ASSOCIATION--COLOBOMA, HEART ANOMALY, CHOANAL ATRESIA, RETARDATION, GENITAL AND EAR ANOMALIES; Coloboma, heart anomaly, choanal atresia, retardation, genital and ear anomalies; CHARGE association; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0008965; MedGen: C0265354; Orphanet: 138; OMIM: 214800

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004466501	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 11, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 29178447, 16199547, 22461308, 25077900, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004466501

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 11, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Phenotype and genotype analysis of a French cohort of 119 patients with CHARGE syndrome.

Legendre M, Abadie V, Attié-Bitach T, Philip N, Busa T, Bonneau D, Colin E, Dollfus H, Lacombe D, Toutain A, Blesson S, Julia S, Martin-Coignard D, Geneviève D, Leheup B, Odent S, Jouk PS, Mercier S, Faivre L, Vincent-Delorme C, Francannet C, Naudion S, et al.

Am J Med Genet C Semin Med Genet. 2017 Dec;175(4):417-430. doi: 10.1002/ajmg.c.31591. Epub 2017 Nov 27.

PubMed [citation]

PMID:: 29178447

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004466501.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Disruption of this splice site has been observed in individuals with CHARGE syndrome (PMID: 29178447; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 20 of the CHD7 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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