VCV000041543.98 - ClinVar

NM_000059.4(BRCA2):c.1792A>G (p.Thr598Ala)

Germline

Top reviewed classifications are shown here.

Submission summary:

37 submissions

36 submitters

9 conditions

Reviewed by expert panel

Benign

Jun 2019 by Evidence-based…

for Breast-ovarian cancer, familial, susceptibility to, 2

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000059.4(BRCA2):c.1792A>G (p.Thr598Ala)

Variation ID: 41543 Accession: VCV000041543.98

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q13.1 13: 32333270 (GRCh38) [ NCBI UCSC ] 13: 32907407 (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 12, 2013	Oct 20, 2024	Jun 18, 2019

HGVS

Nucleotide	Protein	Molecular consequence
NM_000059.4:c.1792A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000050.3:p.Thr598Ala	missense
NC_000013.11:g.32333270A>G
NC_000013.10:g.32907407A>G
NG_012772.3:g.22791A>G
LRG_293:g.22791A>G
LRG_293t1:c.1792A>G	LRG_293p1:p.Thr598Ala
U43746.1:n.2020A>G

... more HGVS ... less HGVS

Protein change

T598A

Other names

p.T598A:ACA>GCA

Canonical SPDI

NC_000013.11:32333269:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

0.00060 (G)

Allele frequency Help The frequency of the allele represented by this VCV record.

Exome Aggregation Consortium (ExAC) 0.00231

1000 Genomes Project 30x 0.00047

1000 Genomes Project 0.00060

Trans-Omics for Precision Medicine (TOPMed) 0.00117

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00146

The Genome Aggregation Database (gnomAD) 0.00182

The Genome Aggregation Database (gnomAD), exomes 0.00221

Links

dbSNP: rs28897710 ClinGen: CA013229 VarSome

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
Gene	OMIM	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	18985	19144

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.
not provided	Benign (5)	criteria provided, multiple submitters, no conflicts	Jun 1, 2024	RCV000034432.45
Hereditary breast ovarian cancer syndrome	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000043885.27
Familial cancer of breast	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Jan 1, 2019	RCV000074516.15
Breast-ovarian cancer, familial, susceptibility to, 2	Benign (12)	reviewed by expert panel	Jun 18, 2019	RCV000112970.26
not specified	Benign/Likely benign (9)	criteria provided, multiple submitters, no conflicts	Jul 31, 2024	RCV000120304.40
Hereditary cancer-predisposing syndrome	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	May 10, 2020	RCV000128961.16
Breast neoplasm	Likely benign (1)	no assertion criteria provided	Jun 1, 2014	RCV000148412.11
Fanconi anemia complementation group D1	Likely benign (1)	criteria provided, single submitter	Mar 6, 2018	RCV001111738.12
Breast and/or ovarian cancer	Benign (1)	criteria provided, single submitter	Apr 21, 2016	RCV000768623.10

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 (ENIGMA BRCA1/2 Classification Criteria (2017-06-29)) 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: SCV001161527.2 First in ClinVar: Feb 17, 2020 Last updated: Jan 07, 2023	Publications: PubMed (1) PubMed: 31131967 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 = 0.000045 (less)
Likely benign (Jan 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: no Allele origin: germline	Genetic Services Laboratory, University of Chicago Accession: SCV002068977.1 First in ClinVar: Jan 29, 2022 Last updated: Jan 29, 2022
Benign (May 10, 2020)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002533263.1 First in ClinVar: Mar 25, 2020 Last updated: Mar 25, 2020
Benign (Nov 03, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: not provided Allele origin: germline	Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden Accession: SCV002010733.3 First in ClinVar: Nov 06, 2021 Last updated: Jul 16, 2023
Benign (Jul 31, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002550288.6 First in ClinVar: Jul 30, 2022 Last updated: Aug 04, 2024
Benign (Jan 22, 2014)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Familial cancer of breast Affected status: yes Allele origin: germline	GeneDx Accession: SCV000108601.3 First in ClinVar: Dec 10, 2013 Last updated: Feb 24, 2015	Comment: The variant is found in BRCA1-BRCA2,PANC-HEREDIC,BR-OV-HEREDIC,HIRISK-BR-HEREDIC,ENDOM-HEREDIC panel(s).
Likely benign (Mar 28, 2016)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000538470.1 First in ClinVar: Oct 22, 2016 Last updated: Oct 22, 2016	Comment: Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or … (more) Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.8% (53/6604) Finnish chromosomes (less) Method: Genome/Exome Filtration
Benign (Jan 16, 2015)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000224753.5 First in ClinVar: Jun 28, 2015 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2 Number of individuals with the variant: 3 Sex: mixed
Likely benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000383639.3 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Benign (Oct 02, 2020)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: unknown Allele origin: germline	Johns Hopkins Genomics, Johns Hopkins University Accession: SCV001438364.1 First in ClinVar: Oct 25, 2020 Last updated: Oct 25, 2020
Likely benign (Jan 01, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial cancer of breast Affected status: yes Allele origin: unknown	Institute of Human Genetics, University of Leipzig Medical Center Accession: SCV001440081.1 First in ClinVar: Oct 31, 2020 Last updated: Oct 31, 2020
Benign (Jun 15, 2020)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV001470403.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021	Publications: PubMed (3) PubMed: 12215251‚ 24728327‚ 31131967
Benign (Jun 01, 2024)	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2) Method: clinical testing	not provided Affected status: yes Allele origin: germline	CeGaT Center for Human Genetics Tuebingen Accession: SCV000892064.28 First in ClinVar: Mar 31, 2019 Last updated: Oct 20, 2024	Comment: BRCA2: BP1, BP4, BS3:Supporting, BS1 Number of individuals with the variant: 23
Benign (Nov 03, 2014)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Michigan Medical Genetics Laboratories, University of Michigan Accession: SCV000195963.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014	Tissue: Blood
Benign (Oct 09, 2014)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Study: VKGL Data-share Consensus Accession: SCV000743265.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Sep 21, 2015)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000744416.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (Apr 21, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast and/or ovarian cancer Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Study: Canadian Open Genetics Repository Accession: SCV000219306.4 First in ClinVar: Mar 29, 2015 Last updated: May 06, 2019
Likely benign (May 28, 2019)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV001139010.1 First in ClinVar: Jan 13, 2020 Last updated: Jan 13, 2020
Likely benign (Mar 06, 2018)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Fanconi anemia complementation group D1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV001269322.1 First in ClinVar: May 31, 2020 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. (less)
Likely benign (Nov 01, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Hereditary breast ovarian cancer syndrome Affected status: yes Allele origin: germline	Genetics Program, Instituto Nacional de Cancer Accession: SCV002515251.1 First in ClinVar: Nov 19, 2022 Last updated: Nov 19, 2022	Publications: PubMed (1) PubMed: 36329109 Geographic origin: Brazil
Likely benign (Feb 15, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Color Diagnostics, LLC DBA Color Health Accession: SCV000683448.2 First in ClinVar: Feb 19, 2018 Last updated: Dec 11, 2022
Likely benign (Feb 19, 2014)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: literature only	Breast-ovarian cancer, familial 2 (Autosomal dominant inheritance) Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000154076.2 First in ClinVar: Jun 09, 2014 Last updated: Dec 24, 2022	Publications: PubMed (10) PubMed: 12845657‚ 21520273‚ 21702907‚ 22703879‚ 24055113‚ 21232165‚ 18284688‚ 12215251‚ 16683254‚ 21952622
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000071898.15 First in ClinVar: Jul 03, 2013 Last updated: Feb 20, 2024
Benign (Sep 22, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000602855.4 First in ClinVar: Aug 27, 2017 Last updated: Feb 20, 2024
Benign (Nov 19, 2014)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000172842.7 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	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000733234.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Study: VKGL Data-share Consensus Accession: SCV001799062.1 First in ClinVar: Aug 21, 2021 Last updated: Aug 21, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001958923.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (Mar 02, 2020)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	BRCAlab, Lund University Accession: SCV004244230.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
variant of unknown significance (Jul 13, 2012)	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: SCV000043199.1 First in ClinVar: Apr 12, 2013 Last updated: Apr 12, 2013	Publications: PubMed (1) PubMed: 22703879 Comment: Converted during submission to Uncertain significance. Number of individuals with the variant: 2 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)
Likely benign (Jun 01, 2014)	no assertion criteria provided Method: research	Breast cancer (Autosomal dominant inheritance) Affected status: unknown Allele origin: germline	CSER _CC_NCGL, University of Washington Study: ESP 6500 variant annotation Accession: SCV000190111.1 First in ClinVar: Dec 06, 2014 Last updated: Dec 06, 2014 Comment: Variants classified for the Actionable exomic incidental findings in 6503 participants: challenges of variant classification manuscript
Likely benign (Dec 18, 2017)	no assertion criteria provided Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV000778648.1 First in ClinVar: Oct 20, 2014 Last updated: Oct 20, 2014
Likely benign (Apr 27, 2018)	no assertion criteria provided Method: clinical testing	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	True Health Diagnostics Accession: SCV000805237.1 First in ClinVar: May 03, 2018 Last updated: May 03, 2018
Benign (-)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 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: SCV000591767.2 First in ClinVar: Aug 27, 2017 Last updated: Apr 13, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001906237.1 First in ClinVar: Sep 23, 2021 Last updated: Sep 23, 2021
not provided (-)	no classification provided Method: clinical testing	Breast-ovarian cancer, familial 2 Affected status: yes Allele origin: germline	Breast Cancer Information Core (BIC) (BRCA2) Accession: SCV000145936.1 First in ClinVar: Apr 01, 2014 Last updated: Apr 01, 2014	Observation 1: Number of individuals with the variant: 28 Observation 2: Number of individuals with the variant: 1 Geographic origin: Central/Eastern European Observation 3: Number of individuals with the variant: 6 Geographic origin: Western European Observation 4: Number of individuals with the variant: 4 Ethnicity/Population group: Ashkenazi Observation 5: Number of individuals with the variant: 1 Ethnicity/Population group: Ashkenazi, Central/Eastern European Observation 6: Number of individuals with the variant: 1 Ethnicity/Population group: Caucasian Geographic origin: Germany Observation 7: Number of individuals with the variant: 1 Ethnicity/Population group: Caucasian Geographic origin: Spain Observation 8: Number of individuals with the variant: 2 Ethnicity/Population group: Central/Eastern European Observation 9: Number of individuals with the variant: 1 Ethnicity/Population group: Dutch Observation 10: Number of individuals with the variant: 1 Ethnicity/Population group: French Canadian Observation 11: Number of individuals with the variant: 1 Ethnicity/Population group: Latin American, Caribbean Observation 12: Number of individuals with the variant: 1 Ethnicity/Population group: Native American, Central/Eastern European, L Observation 13: Number of individuals with the variant: 1 Ethnicity/Population group: Polish, Central/Eastern European Observation 14: Number of individuals with the variant: 13 Ethnicity/Population group: Western European Observation 15: Number of individuals with the variant: 1 Ethnicity/Population group: Western, Central/Eastern European
not provided (Sep 19, 2013)	no classification provided Method: reference population	AllHighlyPenetrant Affected status: unknown Allele origin: germline	ITMI Accession: SCV000084456.1 First in ClinVar: Jun 09, 2014 Last updated: Jun 09, 2014 Comment: Please see associated publication for description of ethnicities	Publications: PubMed (1) PubMed: 24728327 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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Comment:

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: ExAC: 0.8% (53/6604) Finnish chromosomes

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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely 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.

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:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service.	Matta BP	Scientific reports	2022	PMID: 36329109
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
Germline variation in cancer-susceptibility genes in a healthy, ancestrally diverse cohort: implications for individual genome sequencing.	Bodian DL	PloS one	2014	PMID: 24728327
Actionable, pathogenic incidental findings in 1,000 participants' exomes.	Dorschner MO	American journal of human genetics	2013	PMID: 24055113
Secondary variants in individuals undergoing exome sequencing: screening of 572 individuals identifies high-penetrance mutations in cancer-susceptibility genes.	Johnston JJ	American journal of human genetics	2012	PMID: 22703879
BRCA2 is a moderate penetrance gene contributing to young-onset prostate cancer: implications for genetic testing in prostate cancer patients.	Kote-Jarai Z	British journal of cancer	2011	PMID: 21952622
A high-throughput protocol for mutation scanning of the BRCA1 and BRCA2 genes.	Hondow HL	BMC cancer	2011	PMID: 21702907
Assessment of rare BRCA1 and BRCA2 variants of unknown significance using hierarchical modeling.	Capanu M	Genetic epidemiology	2011	PMID: 21520273
The occurrence of germline BRCA1 and BRCA2 sequence alterations in Slovenian population.	Stegel V	BMC medical genetics	2011	PMID: 21232165
Evaluation of unclassified variants in the breast cancer susceptibility genes BRCA1 and BRCA2 using five methods: results from a population-based study of young breast cancer patients.	Lee E	Breast cancer research : BCR	2008	PMID: 18284688
A DGGE system for comprehensive mutation screening of BRCA1 and BRCA2: application in a Dutch cancer clinic setting.	van der Hout AH	Human mutation	2006	PMID: 16683254
Prevalence of BRCA1 and BRCA2 germline mutations in young breast cancer patients: a population-based study.	de Sanjosé S	International journal of cancer	2003	PMID: 12845657
Characterization of common BRCA1 and BRCA2 variants.	Deffenbaugh AM	Genetic testing	2002	PMID: 12215251
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=BRCA2	-	-	-	-
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Text-mined citations for rs28897710 ...

These 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 25, 2024

ClinVar Genomic variation as it relates to human health

NM_000059.4(BRCA2):c.1792A>G (p.Thr598Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs28897710 ...