ClinVar Genomic variation as it relates to human health
NM_017780.4(CHD7):c.2053_2058dup (p.Ala685_Lys686dup)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_017780.4(CHD7):c.2053_2058dup (p.Ala685_Lys686dup)
Variation ID: 95776 Accession: VCV000095776.48
- Type and length
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Duplication, 6 bp
- Location
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Cytogenetic: 8q12.2 8: 60781383-60781384 (GRCh38) [ NCBI UCSC ] 8: 61693942-61693943 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Oct 5, 2015 Oct 20, 2024 Aug 1, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017780.4:c.2053_2058dup MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060250.2:p.Ala685_Lys686dup NM_001316690.1:c.1716+337_1716+342dup NM_017780.3:c.2053_2058dupGCAAAA NC_000008.11:g.60781387_60781392dup NC_000008.10:g.61693946_61693951dup NG_007009.1:g.107608_107613dup LRG_176:g.107608_107613dup - Protein change
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- Other names
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p.Ala685_Lys686dup
- Canonical SPDI
- NC_000008.11:60781383:AAAGCAAAA:AAAGCAAAAGCAAAA
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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0.00339 (AAAGCAAAAGCAAAA)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CHD7 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3372 | 3581 | |
LOC126860403 | - | - | - | GRCh38 | - | 190 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
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Apr 10, 2018 | RCV000081821.34 | |
Likely benign (1) |
criteria provided, single submitter
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Jun 14, 2016 | RCV000266990.13 | |
Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
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Jan 29, 2024 | RCV000233607.23 | |
Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
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Aug 1, 2024 | RCV000514792.28 | |
Benign (1) |
criteria provided, single submitter
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Jul 20, 2016 | RCV002313798.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Likely benign
(Feb 08, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000247015.1
First in ClinVar: Oct 05, 2015 Last updated: Oct 05, 2015 |
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Benign
(Jul 10, 2015)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
unknown
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Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000258119.2
First in ClinVar: Dec 27, 2015 Last updated: Dec 27, 2015 |
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Likely benign
(Jun 14, 2016)
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criteria provided, single submitter
Method: clinical testing
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Kallmann Syndrome
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000474401.2
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
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Likely benign
(Nov 01, 2016)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
Affected status: yes
Allele origin:
germline
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Center for Human Genetics, Inc, Center for Human Genetics, Inc
Accession: SCV000781104.1
First in ClinVar: Jul 07, 2018 Last updated: Jul 07, 2018 |
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Benign
(Dec 06, 2013)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000202451.3
First in ClinVar: Jan 29, 2015 Last updated: May 03, 2018 |
Sex: mixed
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Benign
(Jan 18, 2019)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Athena Diagnostics
Accession: SCV001143546.1
First in ClinVar: Jan 18, 2020 Last updated: Jan 18, 2020 |
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Benign
(Dec 07, 2016)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001859851.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 29304373, 28475860, 25077900)
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Benign
(Jul 20, 2016)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000848028.5
First in ClinVar: Nov 08, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more)
This alteration is classified as 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. (less)
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Likely benign
(Aug 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004032817.11
First in ClinVar: Sep 16, 2023 Last updated: Oct 20, 2024 |
Comment:
CHD7: PM4, BS1, BS2
Number of individuals with the variant: 37
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Benign
(-)
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criteria provided, single submitter
Method: clinical testing
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NOT SPECIFIED
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV000312949.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
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Benign
(Apr 12, 2017)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: not provided
Allele origin:
germline
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Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics
Accession: SCV000610071.1
First in ClinVar: Nov 06, 2017 Last updated: Nov 06, 2017 |
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Benign
(Apr 10, 2018)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966269.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
p.Ala685_Lys686dup (c.2053_2058dupGCAAAA) in exon 3 of CHD7: This variant is cla ssified as benign because it has been identified in 1% of European chromosomes, including … (more)
p.Ala685_Lys686dup (c.2053_2058dupGCAAAA) in exon 3 of CHD7: This variant is cla ssified as benign because it has been identified in 1% of European chromosomes, including 4 homozygotes, by the Genome Aggregation Database (gnomAD; http://gnom ad.broadinstitute.org; dbSNP rs377139749). ACMG/AMP Criteria applied: BA1. (less)
Number of individuals with the variant: 3
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Benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001137628.1
First in ClinVar: Jan 11, 2020 Last updated: Jan 11, 2020 |
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Benign
(Jan 29, 2024)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000290338.9
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001920935.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001927609.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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not specified
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001964276.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Likely benign
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001743420.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021 |
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Genomic DNA Methylation Signatures Enable Concurrent Diagnosis and Clinical Genetic Variant Classification in Neurodevelopmental Syndromes. | Aref-Eshghi E | American journal of human genetics | 2018 | PMID: 29304373 |
CHARGE and Kabuki Syndromes: Gene-Specific DNA Methylation Signatures Identify Epigenetic Mechanisms Linking These Clinically Overlapping Conditions. | Butcher DT | American journal of human genetics | 2017 | PMID: 28475860 |
The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients. | Marcos S | The Journal of clinical endocrinology and metabolism | 2014 | PMID: 25077900 |
Mutation update on the CHD7 gene involved in CHARGE syndrome. | Janssen N | Human mutation | 2012 | PMID: 22461308 |
Mutations in the CHD7 gene: the experience of a commercial laboratory. | Bartels CF | Genetic testing and molecular biomarkers | 2010 | PMID: 21158681 |
CHD7 mutation spectrum in 28 Swedish patients diagnosed with CHARGE syndrome. | Wincent J | Clinical genetics | 2008 | PMID: 18445044 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CHD7 | - | - | - | - |
Text-mined citations for rs377139749 ...
HelpRecord last updated Nov 25, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.