p.Leu2806Val in exon 38 of CHD7: This variant is classified as likely benign bec ause it has been identified in 0.37% (85/22966) of African chromosomes (included in 322/269740 total chromosomes) by the Genome Aggregation Database (gnomAD, ht tp://gnomad.broadinstitute.org; dbSNP rs45521933). ACMG/AMP Criteria applied: BS 1.
ClinVar Genomic variation as it relates to human health
NM_017780.4(CHD7):c.8416C>G (p.Leu2806Val)
Germline
Classification
Help
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.
(13)
Help
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.
Benign/Likely benign
13
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_017780.4(CHD7):c.8416C>G (p.Leu2806Val)
Variation ID: 95814 Accession: VCV000095814.46
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 8q12.2 8: 60865355 (GRCh38) [ NCBI UCSC ] 8: 61777914 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Nov 23, 2014 Oct 20, 2024 Feb 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_017780.4:c.8416C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_060250.2:p.Leu2806Val missense NM_001316690.1:c.2269C>G NP_001303619.1:p.Leu757Val missense NC_000008.11:g.60865355C>G NC_000008.10:g.61777914C>G NG_007009.1:g.191576C>G LRG_176:g.191576C>G LRG_176t1:c.8416C>G LRG_176p1:p.Leu2806Val Q9P2D1:p.Leu2806Val - Protein change
- L2806V, L757V
- Other names
- -
- Canonical SPDI
- NC_000008.11:60865354:C:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00140 (G)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 30x 0.00187
Trans-Omics for Precision Medicine (TOPMed) 0.00204
The Genome Aggregation Database (gnomAD), exomes 0.00123
Exome Aggregation Consortium (ExAC) 0.00124
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00129
1000 Genomes Project 0.00140
The Genome Aggregation Database (gnomAD) 0.00176
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| CHD7 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
3368 | 3577 | |
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. |
|---|---|---|---|---|
| Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jun 5, 2018 | RCV000145699.26 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 29, 2024 | RCV000282690.21 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 12, 2018 | RCV000349365.13 | |
| Benign/Likely benign (6) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000590628.25 | |
| Benign (1) |
criteria provided, single submitter
|
Mar 26, 2019 | RCV002311675.9 | |
|
CHD7-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
Feb 25, 2020 | RCV003925074.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(Apr 03, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000113795.8
First in ClinVar: Jan 23, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 3
Sex: mixed
|
|
|
Likely benign
(May 18, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000966398.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
Comment:
p.Leu2806Val in exon 38 of CHD7: This variant is classified as likely benign bec ause it has been identified in 0.37% (85/22966) of African chromosomes … (more)
p.Leu2806Val in exon 38 of CHD7: This variant is classified as likely benign bec ause it has been identified in 0.37% (85/22966) of African chromosomes (included in 322/269740 total chromosomes) by the Genome Aggregation Database (gnomAD, ht tp://gnomad.broadinstitute.org; dbSNP rs45521933). ACMG/AMP Criteria applied: BS 1. (less)
Number of individuals with the variant: 1
|
|
|
Benign
(Jan 12, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Kallmann Syndrome 5
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000474517.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated … (more)
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. (less)
|
|
|
Likely benign
(Jun 05, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV000192807.2
First in ClinVar: Nov 23, 2014 Last updated: Jun 15, 2020 |
|
|
|
Likely benign
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
CHARGE syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000562408.9
First in ClinVar: Dec 06, 2016 Last updated: Feb 14, 2024 |
|
|
|
Benign
(Mar 26, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000847252.5
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)
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005225797.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Likely benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010787.12
First in ClinVar: Jul 16, 2023 Last updated: Oct 20, 2024 |
Comment:
CHD7: BS1
Number of individuals with the variant: 8
|
|
|
Likely benign
(Jan 25, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000699441.1
First in ClinVar: Mar 17, 2018 Last updated: Mar 17, 2018 |
|
|
|
Benign
(Dec 09, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000714566.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
This variant is associated with the following publications: (PMID: 29255181, 31200363, 18073582, 21158681, 22033296, 31628846)
|
|
|
Likely benign
(Feb 25, 2020)
|
no assertion criteria provided
Method: clinical testing
|
CHD7-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004745742.2
First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024 |
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)
Study: VKGL Data-share Consensus
Accession: SCV001799855.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
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: SCV001966663.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
|
|
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Comment:
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
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 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.
Comment:
CHD7: BS1
Comment:
This variant is associated with the following publications: (PMID: 29255181, 31200363, 18073582, 21158681, 22033296, 31628846)
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
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. |
Comment:
p.Leu2806Val in exon 38 of CHD7: This variant is classified as likely benign bec ause it has been identified in 0.37% (85/22966) of African chromosomes (included in 322/269740 total chromosomes) by the Genome Aggregation Database (gnomAD, ht tp://gnomad.broadinstitute.org; dbSNP rs45521933). ACMG/AMP Criteria applied: BS 1.
Comment:
This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
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 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.
Comment:
CHD7: BS1
Comment:
This variant is associated with the following publications: (PMID: 29255181, 31200363, 18073582, 21158681, 22033296, 31628846)
Comment:
This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Next-generation sequencing of patients with congenital anosmia. | Alkelai A | European journal of human genetics : EJHG | 2017 | PMID: 29255181 |
| The diagnostic value of next generation sequencing in familial nonsyndromic congenital heart defects. | Jia Y | American journal of medical genetics. Part A | 2015 | PMID: 25931334 |
| A novel classification system to predict the pathogenic effects of CHD7 missense variants in CHARGE syndrome. | Bergman JE | Human mutation | 2012 | PMID: 22539353 |
| Mutation update on the CHD7 gene involved in CHARGE syndrome. | Janssen N | Human mutation | 2012 | PMID: 22461308 |
| Complete screening of 50 patients with CHARGE syndrome for anomalies in the CHD7 gene using a denaturing high-performance liquid chromatography-based protocol: new guidelines and a proposal for routine diagnosis. | Bilan F | The Journal of molecular diagnostics : JMD | 2012 | PMID: 22033296 |
| 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 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=CHD7 | - | - | - | - |
Text-mined citations for rs45521933 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Nov 10, 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.