ClinVar Genomic variation as it relates to human health
NM_000038.6(APC):c.7862C>G (p.Ser2621Cys)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000038.6(APC):c.7862C>G (p.Ser2621Cys)
Variation ID: 41516 Accession: VCV000041516.77
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q22.2 5: 112843456 (GRCh38) [ NCBI UCSC ] 5: 112179153 (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 Apr 12, 2013 Oct 8, 2024 Feb 26, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000038.6:c.7862C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000029.2:p.Ser2621Cys missense NM_001127510.3:c.7862C>G NP_001120982.1:p.Ser2621Cys missense NM_001127511.3:c.7808C>G NP_001120983.2:p.Ser2603Cys missense NM_001354895.2:c.7862C>G NP_001341824.1:p.Ser2621Cys missense NM_001354896.2:c.7916C>G NP_001341825.1:p.Ser2639Cys missense NM_001354897.2:c.7892C>G NP_001341826.1:p.Ser2631Cys missense NM_001354898.2:c.7787C>G NP_001341827.1:p.Ser2596Cys missense NM_001354899.2:c.7778C>G NP_001341828.1:p.Ser2593Cys missense NM_001354900.2:c.7739C>G NP_001341829.1:p.Ser2580Cys missense NM_001354901.2:c.7685C>G NP_001341830.1:p.Ser2562Cys missense NM_001354902.2:c.7589C>G NP_001341831.1:p.Ser2530Cys missense NM_001354903.2:c.7559C>G NP_001341832.1:p.Ser2520Cys missense NM_001354904.2:c.7484C>G NP_001341833.1:p.Ser2495Cys missense NM_001354905.2:c.7382C>G NP_001341834.1:p.Ser2461Cys missense NM_001354906.2:c.7013C>G NP_001341835.1:p.Ser2338Cys missense NC_000005.10:g.112843456C>G NC_000005.9:g.112179153C>G NG_008481.4:g.155936C>G LRG_130:g.155936C>G LRG_130t1:c.7862C>G LRG_130p1:p.Ser2621Cys P25054:p.Ser2621Cys - Protein change
- S2621C, S2603C, S2495C, S2530C, S2639C, S2580C, S2593C, S2596C, S2631C, S2338C, S2461C, S2520C, S2562C
- Other names
- NM_000038.6(APC):c.7862C>G
- Canonical SPDI
- NC_000005.10:112843455:C: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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0.00180 (G)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
1000 Genomes Project 30x 0.00172
1000 Genomes Project 0.00180
The Genome Aggregation Database (gnomAD), exomes 0.00291
Exome Aggregation Consortium (ExAC) 0.00314
Trans-Omics for Precision Medicine (TOPMed) 0.00320
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00331
The Genome Aggregation Database (gnomAD) 0.00358
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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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. |
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Benign/Likely benign (7) |
criteria provided, multiple submitters, no conflicts
|
Aug 1, 2024 | RCV000034401.46 | |
Benign (6) |
criteria provided, multiple submitters, no conflicts
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Jul 31, 2024 | RCV000077995.38 | |
Benign (5) |
criteria provided, multiple submitters, no conflicts
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Aug 4, 2022 | RCV000130974.16 | |
Benign (1) |
criteria provided, single submitter
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Mar 6, 2018 | RCV000367966.13 | |
Benign (5) |
reviewed by expert panel
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Feb 26, 2023 | RCV000987588.17 | |
Benign (1) |
no assertion criteria provided
|
- | RCV001353889.9 |
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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Benign
(Feb 26, 2023)
|
reviewed by expert panel
Method: curation
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Familial adenomatous polyposis 1
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV003836612.1 First in ClinVar: Mar 11, 2023 Last updated: Mar 11, 2023 |
Comment:
The c.7862C>G variant in APC is a missense variant predicted to cause the substitution of Serine by Cysteine at amino acid position 2621 (p.Ser2621Cys). This … (more)
The c.7862C>G variant in APC is a missense variant predicted to cause the substitution of Serine by Cysteine at amino acid position 2621 (p.Ser2621Cys). This variant has been observed in more than 10 heterozygous individuals over the age of 50 with no features of FAP, worth more than 10 healthy individual points (BS2; Ambry internal data). APC is defined by the ClinGen APC VCEP as a gene for which primarily truncating variants are known to cause disease (BP1). The highest population minor allele frequency in the non-cancer cohort of gnomAD v2.1.1 is 0.5021% in the non-Finnish European population, which is higher than the ClinGen APC VCEP threshold of 0.1% for BA1, and therefore meets this criterion (BA1). In summary, this variant meets the criteria to be classified as Benign for FAP based on the ACMG/AMP criteria applied, as specified by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel: BA1, BS2, and BP1 (VCEP specifications version 1; date of approval: 12/12/2022). (less)
|
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Likely Benign
(Jan 24, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
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: SCV000511737.1
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
Converted during submission to Likely benign.
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Benign
(Mar 06, 2018)
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criteria provided, single submitter
Method: clinical testing
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APC-Associated Polyposis Disorders
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000452050.3
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)
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Benign
(Aug 04, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C.
Accession: SCV002819164.1
First in ClinVar: Jan 15, 2023 Last updated: Jan 15, 2023 |
|
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Benign
(Apr 03, 2023)
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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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ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000885018.5
First in ClinVar: May 30, 2018 Last updated: Feb 20, 2024 |
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Benign
(Feb 01, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000562659.9
First in ClinVar: Apr 17, 2017 Last updated: Feb 28, 2024 |
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Benign
(Nov 28, 2014)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000185889.10
First in ClinVar: Aug 06, 2014 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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Benign
(Sep 30, 2013)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000109833.8
First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely benign
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001136953.1
First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020 |
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Benign
(Oct 16, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: no
Allele origin:
germline
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Genetic Services Laboratory, University of Chicago
Accession: SCV000593260.2
First in ClinVar: Oct 02, 2016 Last updated: Jun 15, 2020 |
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Benign
(Mar 03, 2015)
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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: SCV001830306.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
This variant is associated with the following publications: (PMID: 24728327, 27153395, 1316610, 24082139, 21859464, 24599579, 25260786, 22703879)
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Benign
(May 10, 2020)
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criteria provided, single submitter
Method: curation
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002530900.1
First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 |
|
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Likely benign
(-)
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criteria provided, single submitter
Method: not provided
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not provided
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005219895.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
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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: SCV001154486.26
First in ClinVar: Feb 03, 2020 Last updated: Oct 08, 2024 |
Comment:
APC: BP4, BS1, BS2
Number of individuals with the variant: 33
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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: SCV000301607.1
First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016 |
|
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Benign
(Mar 21, 2016)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Color Diagnostics, LLC DBA Color Health
Accession: SCV000681891.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
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Benign
(Nov 03, 2021)
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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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Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden
Accession: SCV002011081.3
First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023 |
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Benign
(Jul 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: yes
Allele origin:
germline
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KCCC/NGS Laboratory, Kuwait Cancer Control Center
Accession: SCV004015958.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
|
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Benign
(Apr 11, 2024)
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criteria provided, single submitter
Method: clinical testing
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Familial adenomatous polyposis 1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV005084436.1
First in ClinVar: Jul 23, 2024 Last updated: Jul 23, 2024 |
Comment:
This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence … (more)
This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. (less)
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Benign
(Jul 31, 2024)
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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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Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550666.6
First in ClinVar: Jul 30, 2022 Last updated: Aug 04, 2024 |
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Likely benign
(Apr 25, 2018)
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no assertion criteria provided
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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True Health Diagnostics
Accession: SCV000805208.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
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Benign
(-)
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no assertion criteria provided
Method: clinical testing
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Carcinoma of colon
Affected status: yes
Allele origin:
unknown
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Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591216.2 First in ClinVar: Oct 02, 2016 Last updated: Apr 13, 2021 |
Comment:
The p.Ser2621Cys variant has been previously reported in the literature. From selected publications it was identified in 7 if 2428 case chromosomes (frequency: 0.0028) and … (more)
The p.Ser2621Cys variant has been previously reported in the literature. From selected publications it was identified in 7 if 2428 case chromosomes (frequency: 0.0028) and 21 of 3670 control chromosomes (frequency: 0.0057), increasing the likelihood this is a benign polymorphism (Miyoshi_1992_1316610, Scott_2004_2839999, Ruiz-Ponte_2001_11668620, Azzopardi_2008_18199528, Lefevre_2012_22875147). In addition, it is reported with a frequency of 126/2172 control chromosomes from the 1000 genomes project and at a frequency of 0.005 in the European gohort ESP project database (dbSNPiD: rs72541816). Furthermore, 2 studies demonstrated non-segregation (Scott_2004_2839999, Ruiz-Ponte_2001_11668620) and the frequency of this variant was reported as higher in controls vs cases in two studies (Cancer Res-2008-Azzopardi-358-63_18199528, Lefevre_2012_jhg201299a_22875147), increasing the likelihood that this variant is benign. This variant is conserved in mammals but not lower organisms although it appears to not be located in an important functional domain, the creation of cystein residues, having a higher propensity for generating disulphide bonds, could in theory impact the protein. Computational analysis using several programs (SIFT, AlignGVGD, Polyphen-2, BLOSUM), do not agree on the imapact this variant change may have, and this information is not very predictive of pathogenicity. Based on the above information, this variant is classified as benign. (less)
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no known pathogenicity
(Jul 13, 2012)
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no assertion criteria provided
Method: research
|
not provided
Affected status: no
Allele origin:
germline
|
Biesecker Lab/Clinical Genomics Section, National Institutes of Health
Study: ClinSeq
Accession: SCV000043143.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013 |
Comment:
Converted during submission to Benign.
Number of individuals with the variant: 6
Comment on evidence:
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for … (more)
The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:22703879 for details. (less)
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Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Mayo Clinic Laboratories, Mayo Clinic
Accession: SCV000691769.1
First in ClinVar: Feb 19, 2018 Last updated: Feb 19, 2018 |
|
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not provided
(Sep 19, 2013)
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no classification provided
Method: reference population
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AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
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ITMI
Accession: SCV000084165.1
First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014
Comment:
Please see associated publication for description of ethnicities
|
Observation 1:
Ethnicity/Population group: Whole_cohort
Observation 2:
Ethnicity/Population group: African
Observation 3:
Ethnicity/Population group: African_European
Observation 4:
Ethnicity/Population group: Central_Asian
Observation 5:
Ethnicity/Population group: East_Asian
Observation 6:
Ethnicity/Population group: European
Observation 7:
Ethnicity/Population group: Hispanic
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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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http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=APC | - | - | - | - |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/cc19eee0-403e-47f1-acab-77bd1720f3ed | - | - | - | - |
Text-mined citations for rs72541816 ...
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.