IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000603
ClinVar Genomic variation as it relates to human health
NM_000059.4(BRCA2):c.440A>G (p.Gln147Arg)
Germline
Top reviewed classifications are shown here.
Submission summary:
Reviewed by expert panel
Benign
Jun 2019 by
Evidence-based…
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000059.4(BRCA2):c.440A>G (p.Gln147Arg)
Variation ID: 51644 Accession: VCV000051644.47
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 13q13.1 13: 32326115 (GRCh38) [ NCBI UCSC ] 13: 32900252 (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 Apr 1, 2014 May 1, 2024 Jun 18, 2019 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000059.4:c.440A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000050.3:p.Gln147Arg missense NC_000013.11:g.32326115A>G NC_000013.10:g.32900252A>G NG_012772.3:g.15636A>G LRG_293:g.15636A>G LRG_293t1:c.440A>G LRG_293p1:p.Gln147Arg U43746.1:n.668A>G - Protein change
- Q147R
- Other names
-
p.Q147R:CAA>CGA
NP_000050.3:p.Gln147Arg
668A>G
- Canonical SPDI
- NC_000013.11:32326114:A: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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Exome Aggregation Consortium (ExAC) 0.00025
The Genome Aggregation Database (gnomAD) 0.00025
Trans-Omics for Precision Medicine (TOPMed) 0.00024
- 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. |
|||
| BRCA2 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
18962 | 19121 | |
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. |
|---|---|---|---|---|
| Benign (2) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2024 | RCV000044408.28 | |
| Benign (7) |
reviewed by expert panel
|
Jun 18, 2019 | RCV000077324.25 | |
| Benign/Likely benign (5) |
criteria provided, multiple submitters, no conflicts
|
Aug 15, 2023 | RCV000120385.28 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jun 25, 2020 | RCV000131281.16 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000349768.13 | |
| Benign/Likely benign (3) |
criteria provided, multiple submitters, no conflicts
|
Oct 27, 2023 | RCV000679172.26 | |
| Uncertain significance (1) |
no assertion criteria provided
|
Jan 16, 2017 | RCV000677867.9 | |
| Benign (1) |
no assertion criteria provided
|
- | RCV001353994.9 | |
| Likely benign (1) |
no assertion criteria provided
|
- | RCV002250513.9 | |
| Benign (1) |
criteria provided, single submitter
|
Jan 1, 2022 | RCV003153335.9 | |
| Likely benign (1) |
criteria provided, single submitter
|
Sep 28, 2022 | RCV003492350.1 | |
| click to load more click to collapse | ||||
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. |
|
|---|---|---|---|---|---|
|
Benign
(Jun 18, 2019)
|
reviewed by expert panel
Method: curation
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)
Accession: SCV001161532.2
First in ClinVar: Feb 16, 2020 Last updated: Jan 07, 2023 |
Comment:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on … (more)
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000603 (less)
|
|
|
Benign
(Apr 18, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Cancer Genetics and Genomics Laboratory, British Columbia Cancer Agency
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000586916.1 First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016 |
|
|
|
Likely benign
(Jul 07, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
PreventionGenetics, part of Exact Sciences
Accession: SCV000805706.1
First in ClinVar: Sep 14, 2018 Last updated: Sep 14, 2018 |
|
|
|
Likely benign
(Nov 21, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: no
Allele origin:
germline
|
Genetic Services Laboratory, University of Chicago
Accession: SCV002068188.1
First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022 |
|
|
|
Benign
(Jun 25, 2020)
|
criteria provided, single submitter
Method: curation
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Sema4, Sema4
Accession: SCV002533868.1
First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020 |
|
|
|
Likely benign
(Aug 09, 2014)
|
criteria provided, single submitter
Method: literature only
|
Breast-ovarian cancer, familial 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220584.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
|
Benign
(Mar 31, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Quest Diagnostics Nichols Institute San Juan Capistrano
Accession: SCV000887817.3
First in ClinVar: Feb 17, 2019 Last updated: Dec 31, 2022 |
|
|
|
Benign
(Aug 15, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital
Accession: SCV002550250.4
First in ClinVar: Jul 30, 2022 Last updated: Aug 18, 2023 |
|
|
|
Likely benign
(Sep 28, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Breast and/or ovarian cancer
Affected status: unknown
Allele origin:
germline
|
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
Accession: SCV004240311.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000072421.16
First in ClinVar: Jul 03, 2013 Last updated: Feb 14, 2024 |
|
|
|
Likely benign
(Oct 27, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV000602867.4
First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024 |
|
|
|
Benign
(May 28, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
unknown
|
Mendelics
Accession: SCV001138959.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Fanconi anemia complementation group D1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383613.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000383612.3
First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Benign
(Apr 19, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary breast ovarian cancer syndrome
Affected status: yes
Allele origin:
germline
|
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State
Accession: SCV002504837.1
First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022 |
Number of individuals with the variant: 1
Geographic origin: South Africa
|
|
|
Likely benign
(Apr 07, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Color Diagnostics, LLC DBA Color Health
Accession: SCV000683619.2
First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022 |
|
|
|
Benign
(Nov 30, 2018)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000210544.12
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 28961279, 24489791, 22126563, 26067864, 24728327, 28222693, 17972177, 14973102, 17657584, 18627636, 20215541, 21218378, 31360874)
|
|
|
Benign
(Jan 01, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Ovarian cancer
Affected status: yes
Allele origin:
germline
|
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University
Accession: SCV003843273.1
First in ClinVar: Mar 26, 2023 Last updated: Mar 26, 2023 |
|
|
|
Likely Benign
(Feb 05, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Breast-ovarian cancer, familial, susceptibility to, 2
(Autosomal dominant inheritance)
Affected status: unknown
Allele origin:
germline
|
All of Us Research Program, National Institutes of Health
Accession: SCV004846773.1
First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024
Comment:
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more)
This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)
|
Number of individuals with the variant: 26
|
|
|
Benign
(Nov 19, 2014)
|
criteria provided, single submitter
Method: clinical testing
|
Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV000186250.7
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)
|
|
|
Benign
(-)
|
no assertion criteria provided
Method: clinical testing
|
Malignant tumor of breast
Affected status: yes
Allele origin:
unknown
|
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV000591684.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021 |
Comment:
The p.Gln147Arg variant was identified in the literature in at least 2 of 96 proband chromosomes in individuals with Esophageal squamous cell cancer or cervical … (more)
The p.Gln147Arg variant was identified in the literature in at least 2 of 96 proband chromosomes in individuals with Esophageal squamous cell cancer or cervical cancer (Zhong 2011, Kwong 2008). However, a second variant (c.7806-9T>G) was demonstrated to cause aberrant splicing and considered pathogenic was identified in the individual with cervical cancer and shown to segregate together with the p.Gln147Arg variant in at least 2 other affected family members and not in one unaffected family member, increasing the likelihood that the p.Gln147Arg variant does not have clinical significance. This residue is not conserved in mammals and the variant amino acid Arginine (Arg) is present in rat, mouse, dog, cat, opossum and chicken. Computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, increasing the likelihood this variant does not have clinical significance. The variant was identified in individuals of Asian background and our laboratory has tested a limited number of individuals from this population group such that this variant may prove to be a common or rare polymorphism in this population of origin. Furthermore, Myriad calls this variant a polymorphism (personal communication). Based on the above information this variant is considered benign. (less)
Number of individuals with the variant: 13
|
|
|
Uncertain significance
(May 29, 2002)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: yes
Allele origin:
germline
|
Breast Cancer Information Core (BIC) (BRCA2)
Accession: SCV000146864.1
First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014 |
Observation 1:
Number of individuals with the variant: 4
Observation 2:
Number of individuals with the variant: 4
Ethnicity/Population group: Asian
Observation 3:
Number of individuals with the variant: 1
Ethnicity/Population group: Asian, Filipino
Observation 4:
Number of individuals with the variant: 1
Ethnicity/Population group: Chinese
Geographic origin: Malaysia
Observation 5:
Number of individuals with the variant: 3
Ethnicity/Population group: Malay
Geographic origin: Malaysia
Observation 6:
Number of individuals with the variant: 1
Ethnicity/Population group: Philipeno
Observation 7:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European
Observation 8:
Number of individuals with the variant: 1
Ethnicity/Population group: Western European, Native American
|
|
|
Benign
(Feb 19, 2009)
|
no assertion criteria provided
Method: clinical testing
|
Breast-ovarian cancer, familial 2
Affected status: not provided
Allele origin:
germline
|
Sharing Clinical Reports Project (SCRP)
Accession: SCV000109121.4
First in ClinVar: Dec 23, 2013 Last updated: May 27, 2015 |
|
|
|
Uncertain significance
(Jan 16, 2017)
|
no assertion criteria provided
Method: clinical testing
|
Cancer of the pancreas
Affected status: yes
Allele origin:
germline
|
3DMed Clinical Laboratory Inc
Accession: SCV000804028.1
First in ClinVar: Aug 27, 2018 Last updated: Aug 27, 2018 |
|
|
|
Likely benign
(-)
|
no assertion criteria provided
Method: literature only
|
Familial cancer of breast
Affected status: yes
Allele origin:
germline
|
Center for Precision Medicine, Meizhou People's Hospital
Accession: SCV002520926.1
First in ClinVar: Jun 05, 2022 Last updated: Jun 05, 2022 |
|
|
|
not provided
(Sep 19, 2013)
|
no classification provided
Method: reference population
|
AllHighlyPenetrant
Affected status: unknown
Allele origin:
germline
|
ITMI
Accession: SCV000084537.1
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
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 28961279, 24489791, 22126563, 26067864, 24728327, 28222693, 17972177, 14973102, 17657584, 18627636, 20215541, 21218378, 31360874)
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:
The p.Gln147Arg variant was identified in the literature in at least 2 of 96 proband chromosomes in individuals with Esophageal squamous cell cancer or cervical cancer (Zhong 2011, Kwong 2008). However, a second variant (c.7806-9T>G) was demonstrated to cause aberrant splicing and considered pathogenic was identified in the individual with cervical cancer and shown to segregate together with the p.Gln147Arg variant in at least 2 other affected family members and not in one unaffected family member, increasing the likelihood that the p.Gln147Arg variant does not have clinical significance. This residue is not conserved in mammals and the variant amino acid Arginine (Arg) is present in rat, mouse, dog, cat, opossum and chicken. Computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, increasing the likelihood this variant does not have clinical significance. The variant was identified in individuals of Asian background and our laboratory has tested a limited number of individuals from this population group such that this variant may prove to be a common or rare polymorphism in this population of origin. Furthermore, Myriad calls this variant a polymorphism (personal communication). Based on the above information this variant is considered benign.
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:
IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.000603
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
This variant is associated with the following publications: (PMID: 28961279, 24489791, 22126563, 26067864, 24728327, 28222693, 17972177, 14973102, 17657584, 18627636, 20215541, 21218378, 31360874)
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:
The p.Gln147Arg variant was identified in the literature in at least 2 of 96 proband chromosomes in individuals with Esophageal squamous cell cancer or cervical cancer (Zhong 2011, Kwong 2008). However, a second variant (c.7806-9T>G) was demonstrated to cause aberrant splicing and considered pathogenic was identified in the individual with cervical cancer and shown to segregate together with the p.Gln147Arg variant in at least 2 other affected family members and not in one unaffected family member, increasing the likelihood that the p.Gln147Arg variant does not have clinical significance. This residue is not conserved in mammals and the variant amino acid Arginine (Arg) is present in rat, mouse, dog, cat, opossum and chicken. Computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, increasing the likelihood this variant does not have clinical significance. The variant was identified in individuals of Asian background and our laboratory has tested a limited number of individuals from this population group such that this variant may prove to be a common or rare polymorphism in this population of origin. Furthermore, Myriad calls this variant a polymorphism (personal communication). Based on the above information this variant is considered benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Large scale multifactorial likelihood quantitative analysis of BRCA1 and BRCA2 variants: An ENIGMA resource to support clinical variant classification. | Parsons MT | Human mutation | 2019 | PMID: 31131967 |
| The frequency of cancer predisposition gene mutations in hereditary breast and ovarian cancer patients in Taiwan: From BRCA1/2 to multi-gene panels. | Sung PL | PloS one | 2017 | PMID: 28961279 |
| Characterization of BRCA1 and BRCA2 variants in multi-ethnic Asian cohort from a Malaysian case-control study. | Lai KN | BMC cancer | 2017 | PMID: 28222693 |
| Epithelial Ovarian Cancer Metastatic to the Central Nervous System and a Family History Concerning for Hereditary Breast and Ovarian Cancer--A Potential Relationship. | Jernigan AM | International journal of gynecological cancer : official journal of the International Gynecological Cancer Society | 2015 | PMID: 26067864 |
| Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing. | Bodian DL | PloS one | 2014 | PMID: 24728327 |
| Multifactorial likelihood assessment of BRCA1 and BRCA2 missense variants confirms that BRCA1:c.122A>G(p.His41Arg) is a pathogenic mutation. | Whiley PJ | PloS one | 2014 | PMID: 24489791 |
| Frequent germline mutation in the BRCA2 gene in esophageal squamous cell carcinoma patients from a low-risk Chinese population. | Zhong L | Asian Pacific journal of cancer prevention : APJCP | 2011 | PMID: 22126563 |
| Detection of BRCA1 and BRCA2 mutations in a selected Hawaii population. | Carney ME | Hawaii medical journal | 2010 | PMID: 21218378 |
| A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients. | Sanz DJ | Clinical cancer research : an official journal of the American Association for Cancer Research | 2010 | PMID: 20215541 |
| Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer. | Thirthagiri E | Breast cancer research : BCR | 2008 | PMID: 18627636 |
| Characterization of the pathogenic mechanism of a novel BRCA2 variant in a Chinese family. | Kwong A | Familial cancer | 2008 | PMID: 17657584 |
| BRCA1 and BRCA2 germline mutation analysis in the Indonesian population. | Purnomosari D | Breast cancer research and treatment | 2007 | PMID: 17972177 |
| BRCA1 and BRCA2 mutations in women from Shanghai China. | Suter NM | Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology | 2004 | PMID: 14973102 |
| The breast cancer information core: database design, structure, and scope. | Szabo C | Human mutation | 2000 | PMID: 10923033 |
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Text-mined citations for rs80358674 ...
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Record last updated Oct 27, 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.