NM_017780.4(CHD7):c.5238C>G (p.Tyr1746Ter) AND CHARGE syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 26, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000558253.5

Allele description [Variation Report for NM_017780.4(CHD7):c.5238C>G (p.Tyr1746Ter)]

NM_017780.4(CHD7):c.5238C>G (p.Tyr1746Ter)

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.5238C>G (p.Tyr1746Ter)

HGVS:

NC_000008.11:g.60848542C>G
NG_007009.1:g.174763C>G
NM_001316690.1:c.1717-13687C>G
NM_017780.4:c.5238C>GMANE SELECT
NP_060250.2:p.Tyr1746Ter
LRG_176:g.174763C>G
NC_000008.10:g.61761101C>G
NM_017780.3:c.5238C>G

Protein change:

Y1746*

Links:

dbSNP: rs1554603151

NCBI 1000 Genomes Browser:

rs1554603151

Molecular consequence:

NM_001316690.1:c.1717-13687C>G - intron variant - [Sequence Ontology: SO:0001627]
NM_017780.4:c.5238C>G - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000631254	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Mar 21, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16400610, 22461308, 28492532
SCV003919723	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 26, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000631254

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Mar 21, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV003919723

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 26, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

Spectrum of CHD7 mutations in 110 individuals with CHARGE syndrome and genotype-phenotype correlation.

Lalani SR, Safiullah AM, Fernbach SD, Harutyunyan KG, Thaller C, Peterson LE, McPherson JD, Gibbs RA, White LD, Hefner M, Davenport SL, Graham JM, Bacino CA, Glass NL, Towbin JA, Craigen WJ, Neish SR, Lin AE, Belmont JW.

Am J Hum Genet. 2006 Feb;78(2):303-14. Epub 2005 Dec 29.

PubMed [citation]

PMID:: 16400610
PMCID:: PMC1380237

Mutation update on the CHD7 gene involved in CHARGE syndrome.

Janssen N, Bergman JE, Swertz MA, Tranebjaerg L, Lodahl M, Schoots J, Hofstra RM, van Ravenswaaij-Arts CM, Hoefsloot LH.

Hum Mutat. 2012 Aug;33(8):1149-60. doi: 10.1002/humu.22086. Epub 2012 Apr 16. Review.

PubMed [citation]

PMID:: 22461308

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000631254.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal at codon 1746 (p.Tyr1746*) of the CHD7 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in CHD7 are known to be pathogenic (PMID: 16400610, 22461308).

#	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

From Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV003919723.1

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

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

Last Updated: Jun 2, 2024

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