ClinVar Genomic variation as it relates to human health
NM_017780.4(CHD7):c.3082A>G (p.Ile1028Val)
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.3082A>G (p.Ile1028Val)
Variation ID: 2022 Accession: VCV000002022.20
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 8q12.2 8: 60822627 (GRCh38) [ NCBI UCSC ] 8: 61735186 (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 Aug 21, 2013 Aug 4, 2024 Apr 25, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_017780.4:c.3082A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060250.2:p.Ile1028Val missense NM_001316690.1:c.1717-39602A>G intron variant NC_000008.11:g.60822627A>G NC_000008.10:g.61735186A>G NG_007009.1:g.148848A>G LRG_176:g.148848A>G LRG_176t1:c.3082A>G LRG_176p1:p.Ile1028Val Q9P2D1:p.Ile1028Val - Protein change
- I1028V
- Other names
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- Canonical SPDI
- NC_000008.11:60822626:A:G
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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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Allele frequency
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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
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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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 |
3403 | 3614 |
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
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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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Pathogenic/Likely pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Apr 25, 2024 | RCV000002100.23 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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Mar 2, 2023 | RCV000081828.21 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 31, 2018 | RCV000763598.10 | |
See cases
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Pathogenic (1) |
criteria provided, single submitter
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May 31, 2022 | RCV004584305.1 |
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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Pathogenic
(Aug 27, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000331477.4
First in ClinVar: Dec 06, 2016 Last updated: Jul 30, 2019 |
Number of individuals with the variant: 1
Zygosity: Single Heterozygote
Sex: mixed
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Pathogenic
(Mar 02, 2023)
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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: SCV000329259.7
First in ClinVar: Dec 06, 2016 Last updated: Mar 11, 2023 |
Comment:
Published functional studies demonstrate a damaging effect; the I1028V variant causes a complete loss of function of CHD7 (Balasubramanian et al., 2014); Not observed at … (more)
Published functional studies demonstrate a damaging effect; the I1028V variant causes a complete loss of function of CHD7 (Balasubramanian et al., 2014); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 20884005, 16155193, 18073582, 25472840, 15300250, 22539353, 26563674, 22461308, 28475860, 21158681, 32914532, 34828433, 33189935) (less)
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Likely pathogenic
(-)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
Affected status: yes
Allele origin:
unknown
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Laboratory of Medical Genetics, University of Torino
Accession: SCV004171100.1
First in ClinVar: Dec 02, 2023 Last updated: Dec 02, 2023 |
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Pathogenic
(Dec 06, 2022)
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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: SCV000755739.6
First in ClinVar: Feb 15, 2018 Last updated: Feb 14, 2024 |
Comment:
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to … (more)
Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 2022). This missense change has been observed in individual(s) with CHARGE syndrome (PMID: 15300250, 16155193, 18073582, 20884005, 21158681, 22539353). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1028 of the CHD7 protein (p.Ile1028Val). Experimental studies have shown that this missense change affects CHD7 function (PMID: 25472840). 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 create or strengthen a splice site. (less)
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Pathogenic
(Apr 25, 2024)
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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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Laboratory of Medical Genetics, National & Kapodistrian University of Athens
Accession: SCV005090978.1
First in ClinVar: Aug 04, 2024 Last updated: Aug 04, 2024 |
Comment:
PS4, PS3, PM1, PM2, PP3- This variant has been reported in ClinVar as Pathogenic by other laboratories (Variation ID 2022).In silico prediction tools estimated that … (more)
PS4, PS3, PM1, PM2, PP3- This variant has been reported in ClinVar as Pathogenic by other laboratories (Variation ID 2022).In silico prediction tools estimated that the variant could be damaging for the protein function/stracture. It is not present in population databases (gnomAD no frequency). It is reported previously as causative (PMID: 15300250, 16155193, 18073582, 20884005, 21158681, 22539353). Functional studies support pathogenic effect (PMID: 25472840). (less)
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Pathogenic
(Oct 31, 2018)
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criteria provided, single submitter
Method: clinical testing
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CHARGE syndrome
Hypogonadotropic hypogonadism 5 with or without anosmia
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000894443.1
First in ClinVar: Mar 31, 2019 Last updated: Mar 31, 2019 |
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Pathogenic
(May 31, 2022)
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criteria provided, single submitter
Method: clinical testing
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see cases
Affected status: yes
Allele origin:
unknown
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Institute of Human Genetics, University Hospital Muenster
Accession: SCV002577988.2
First in ClinVar: Oct 08, 2022 Last updated: Jul 07, 2024 |
Comment:
ACMG categories: PS1,PS4,PM2,PM5
Number of individuals with the variant: 1
Clinical Features:
Hypogonadotropic hypogonadism (present)
Zygosity: Single Heterozygote
Age: 20-29 years
Sex: male
Tissue: blood
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Pathogenic
(Sep 01, 2004)
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no assertion criteria provided
Method: literature only
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CHARGE SYNDROME
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000022258.2
First in ClinVar: Apr 04, 2013 Last updated: Aug 21, 2013 |
Comment on evidence:
In a female patient with CHARGE syndrome (214800), Vissers et al. (2004) described a heterozygous 3082A-G transition in exon 12 of the CHD7 gene that … (more)
In a female patient with CHARGE syndrome (214800), Vissers et al. (2004) described a heterozygous 3082A-G transition in exon 12 of the CHD7 gene that resulted in an ile1028-to-val (I1028V) mutation. The patient had coloboma, retardation of growth and development, and semicircular canal agenesis. The mutation was de novo. (less)
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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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Functionally compromised CHD7 alleles in patients with isolated GnRH deficiency. | Balasubramanian R | Proceedings of the National Academy of Sciences of the United States of America | 2014 | PMID: 25472840 |
A novel classification system to predict the pathogenic effects of CHD7 missense variants in CHARGE syndrome. | Bergman JE | Human mutation | 2012 | PMID: 22539353 |
Anosmia predicts hypogonadotropic hypogonadism in CHARGE syndrome. | Bergman JE | The Journal of pediatrics | 2011 | PMID: 20884005 |
Mutations in the CHD7 gene: the experience of a commercial laboratory. | Bartels CF | Genetic testing and molecular biomarkers | 2010 | PMID: 21158681 |
Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions. | Vuorela P | Genetics in medicine : official journal of the American College of Medical Genetics | 2007 | PMID: 18073582 |
CHARGE syndrome: the phenotypic spectrum of mutations in the CHD7 gene. | Jongmans MC | Journal of medical genetics | 2006 | PMID: 16155193 |
Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. | Vissers LE | Nature genetics | 2004 | PMID: 15300250 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CHD7 | - | - | - | - |
Text-mined citations for rs121434338 ...
HelpRecord last updated Jan 19, 2025
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.