ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.7109G>T (p.Gly2370Val)
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.
Uncertain significance(1); Benign(1); Likely benign(6)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000038.6(APC):c.7109G>T (p.Gly2370Val)
Variation ID: 236640 Accession: VCV000236640.24
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 5q22.2 5: 112178400 (GRCh37) [ NCBI UCSC ] 5: 112842703 (GRCh38) [ 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 Oct 9, 2016 Oct 8, 2024 Apr 8, 2024 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000038.6:c.7109G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Gly2370Val missense NM_001127510.3:c.7109G>T NP_001120982.1:p.Gly2370Val missense NM_001127511.3:c.7055G>T NP_001120983.2:p.Gly2352Val missense NM_001354895.2:c.7109G>T NP_001341824.1:p.Gly2370Val missense NM_001354896.2:c.7163G>T NP_001341825.1:p.Gly2388Val missense NM_001354897.2:c.7139G>T NP_001341826.1:p.Gly2380Val missense NM_001354898.2:c.7034G>T NP_001341827.1:p.Gly2345Val missense NM_001354899.2:c.7025G>T NP_001341828.1:p.Gly2342Val missense NM_001354900.2:c.6986G>T NP_001341829.1:p.Gly2329Val missense NM_001354901.2:c.6932G>T NP_001341830.1:p.Gly2311Val missense NM_001354902.2:c.6836G>T NP_001341831.1:p.Gly2279Val missense NM_001354903.2:c.6806G>T NP_001341832.1:p.Gly2269Val missense NM_001354904.2:c.6731G>T NP_001341833.1:p.Gly2244Val missense NM_001354905.2:c.6629G>T NP_001341834.1:p.Gly2210Val missense NM_001354906.2:c.6260G>T NP_001341835.1:p.Gly2087Val missense NC_000005.10:g.112842703G>T NC_000005.9:g.112178400G>T NG_008481.4:g.155183G>T LRG_130:g.155183G>T - Protein change
- G2352V, G2370V, G2087V, G2269V, G2388V, G2210V, G2311V, G2329V, G2342V, G2380V, G2244V, G2345V, G2279V
- Other names
- -
- Canonical SPDI
- NC_000005.10:112842702:G:T
-
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.
-
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00003
The Genome Aggregation Database (gnomAD) 0.00014
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00015
Trans-Omics for Precision Medicine (TOPMed) 0.00019
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. |
|||
APC | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
14956 | 15094 |
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. |
---|---|---|---|---|
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
|
Apr 8, 2024 | RCV000232680.22 | |
Likely benign (1) |
criteria provided, single submitter
|
Feb 23, 2018 | RCV000236405.12 | |
Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 12, 2022 | RCV000569669.18 | |
Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
Sep 21, 2022 | RCV001705238.9 | |
APC-related disorder
|
Likely benign (1) |
no assertion criteria provided
|
Jun 26, 2024 | RCV003977640.2 |
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. |
|
---|---|---|---|---|---|
Uncertain significance
(Aug 03, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
St. Jude Molecular Pathology, St. Jude Children's Research Hospital
Accession: SCV000891016.2
First in ClinVar: Mar 19, 2019 Last updated: Aug 11, 2021 |
|
|
Likely benign
(Jan 18, 2020)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000292908.8
First in ClinVar: Jul 24, 2016 Last updated: Oct 09, 2016 |
|
|
Likely benign
(Feb 23, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000694108.3
First in ClinVar: Mar 17, 2018 Last updated: Dec 11, 2022 |
Comment:
Variant summary: APC c.7109G>T (p.Gly2370Val) alters a conserved nucleotide resulting in a non-conservative amino acid change located in the basic domain (IPR009234) of the encoded … (more)
Variant summary: APC c.7109G>T (p.Gly2370Val) alters a conserved nucleotide resulting in a non-conservative amino acid change located in the basic domain (IPR009234) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. However, the observed variant frequency within African control individuals in the gnomAD database is approximately 9 fold above the estimated maximal expected allele frequency for a pathogenic variant in APC causing Familial Adenomatous Polyposis phenotype (7.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The c.7109G>T variant has been reported in the literature in one individual with breast cancer (Tung 2015). This report does not provide strong evidence regarding an association of the variant with Familial Adenomatous Polyposis. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all classified the variant as uncertain significance. However, two of these laboratories cite the ESP and ExAC database control frequencies, both of which sample fewer individuals and show a lower frequency for the variant in the general population. Based on the evidence outlined above, the variant was classified as likely benign. (less)
|
|
Likely benign
(Sep 12, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000903488.4
First in ClinVar: May 20, 2019 Last updated: Feb 14, 2024 |
|
|
Likely benign
(Jan 30, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000282814.11
First in ClinVar: Jul 01, 2016 Last updated: Feb 20, 2024 |
|
|
Benign
(Aug 09, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000667254.5
First in ClinVar: Jan 01, 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
(Sep 21, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV004220525.1
First in ClinVar: Jan 06, 2024 Last updated: Jan 06, 2024 |
|
|
Likely benign
(Apr 08, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
|
Myriad Genetics, Inc.
Accession: SCV005084517.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease … (more)
This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. (less)
|
|
Likely benign
(Jun 26, 2024)
|
no assertion criteria provided
Method: clinical testing
|
APC-related condition
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV004791517.2
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).
|
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 |
---|---|---|---|---|
Frequency of mutations in individuals with breast cancer referred for BRCA1 and BRCA2 testing using next-generation sequencing with a 25-gene panel. | Tung N | Cancer | 2015 | PMID: 25186627 |
Text-mined citations for rs140079759 ...
HelpRecord last updated Oct 13, 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.