NM_017780.4(CHD7):c.6079C>T (p.Arg2027Ter) AND CHARGE association

Clinical significance:Pathogenic (Last evaluated: Oct 26, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
6 submissions [Details]
Record status:
current
Accession:
RCV000258088.6

Allele description [Variation Report for NM_017780.4(CHD7):c.6079C>T (p.Arg2027Ter)]

NM_017780.4(CHD7):c.6079C>T (p.Arg2027Ter)

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.6079C>T (p.Arg2027Ter)
HGVS:
  • NC_000008.11:g.60852682C>T
  • NG_007009.1:g.178903C>T
  • NM_001316690.1:c.1717-9547C>T
  • NM_017780.4:c.6079C>TMANE SELECT
  • NP_060250.2:p.Arg2027Ter
  • LRG_176t1:c.6079C>T
  • LRG_176:g.178903C>T
  • NC_000008.10:g.61765241C>T
  • NM_017780.2:c.6079C>T
  • NM_017780.3:c.6079C>T
  • p.[Arg2027*]
Protein change:
R2027*
Links:
dbSNP: rs886040995
NCBI 1000 Genomes Browser:
rs886040995
Molecular consequence:
  • NM_001316690.1:c.1717-9547C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_017780.4:c.6079C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

Condition(s)

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

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000328344Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphiacriteria provided, single submitter
    Pathogenic
    (Sep 5, 2016)
    germlineclinical testing

    DGD_Variant_Analysis_Guidelines.docx,

    SCV000680052SBielas Lab, Department of Human Genetics,University of Michiganno assertion criteria providedPathogenic
    (Oct 27, 2017)
    de novoresearch

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

    SCV000755717Invitaecriteria provided, single submitter
    Pathogenic
    (Oct 26, 2019)
    germlineclinical testing

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

    SCV000786713Broad Institute Rare Disease Group, Broad Institute - Broad Institute Center for Mendelian Genomics (CMG)criteria provided, single submitter
    Pathogenicgermlineresearch

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

    SCV001197958University of Washington Center for Mendelian Genomics, University of Washingtonno assertion criteria providedLikely pathogenicde novoresearch

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

    SCV001244805Victorian Clinical Genetics Services,Murdoch Childrens Research Institutecriteria provided, single submitter
    Pathogenic
    (Apr 26, 2018)
    unknownclinical testing

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

    Description

    Clinical Testing

    SCV000328344

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedde novoyesnot providednot providednot providednot providednot providedresearch
    not providedgermlineyes1not providednot providednot providednot providedclinical testing
    not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
    not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
    Unspecifiedgermlineyes11not providednot providednot providedresearch

    Citations

    PubMed

    CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene.

    Jongmans MC, Admiraal RJ, van der Donk KP, Vissers LE, Baas AF, Kapusta L, van Hagen JM, Donnai D, de Ravel TJ, Veltman JA, Geurts van Kessel A, De Vries BB, Brunner HG, Hoefsloot LH, van Ravenswaaij CM.

    J Med Genet. 2006 Apr;43(4):306-14. Epub 2005 Sep 9.

    PubMed [citation]
    PMID:
    16155193
    PMCID:
    PMC2563221

    Prenatal findings in children with early postnatal diagnosis of CHARGE syndrome.

    Busa T, Legendre M, Bauge M, Quarello E, Bretelle F, Bilan F, Sigaudy S, Gilbert-Dussardier B, Philip N.

    Prenat Diagn. 2016 Jun;36(6):561-7. doi: 10.1002/pd.4825. Epub 2016 May 12.

    PubMed [citation]
    PMID:
    27061523
    See all PubMed Citations (7)

    Details of each submission

    From Genomic Diagnostic Laboratory, Division of Genomic Diagnostics,Children's Hospital of Philadelphia, SCV000328344.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not provided1not providednot providedclinical testingnot provided
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided1not providednot providednot provided

    From SBielas Lab, Department of Human Genetics,University of Michigan, SCV000680052.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedresearch PubMed (1)
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1de novoyesnot providednot providednot providednot providednot providednot providednot provided

    From Invitae, SCV000755717.4

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (5)

    Description

    This sequence change creates a premature translational stop signal (p.Arg2027*) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported de novo in individuals affected with CHARGE (PMID: 16155193, 22461308, 27061523). ClinVar contains an entry for this variant (Variation ID: 267435). Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). For these reasons, this variant has been classified as Pathogenic.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

    From Broad Institute Rare Disease Group, Broad Institute - Broad Institute Center for Mendelian Genomics (CMG), SCV000786713.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1Unspecified1not providednot providedresearch PubMed (1)

    Description

    The heterozygous p.Arg227Ter variant was identified by our study in one individual with CHARGE syndrome. The p.Arg227Ter variant is believed to be pathogenic based on numberous reports by other laboratories in the literature and databases.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1germlineyesnot providednot providednot provided1not provided1not provided

    From University of Washington Center for Mendelian Genomics, University of Washington, SCV001197958.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedresearch PubMed (1)
    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1de novoyesnot providednot providednot providednot providednot providednot providednot provided

    From Victorian Clinical Genetics Services,Murdoch Childrens Research Institute, SCV001244805.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedclinical testing PubMed (1)

    Description

    A heterozygous nonsense variant, NM_017780.3(CHD7):c.6079C>T, has been identified in exon 30 of 38 in the CHD7 gene. The variant is predicted to result in a premature stop codon at position 2027 of the protein, NP_060250.2(CHD7):p.(Arg2027*). The variant is predicted to result in loss of protein function either through truncation (downstream functional domains would be affected) or nonsense-mediated decay, which is a reported mechanism of pathogenicity for this gene. The variant is absent in population databases (gnomAD, dbSNP, 1000G) and has been previously described as pathogenic in multiple individuals with CHARGE syndrome (ClinVar, Jongmans et al., (2016), Busa et al., (2016)). Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

    #SampleMethodObservation
    OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
    1unknownyesnot providednot providednot providednot providednot providednot providednot provided

    Last Updated: May 10, 2021

    Support Center