VCV000051355.51 - ClinVar

NM_000059.4(BRCA2):c.2830A>T (p.Lys944Ter)

Germline

Top reviewed classifications are shown here.

Submission summary:

37 submissions

37 submitters

9 conditions

Reviewed by expert panel

Pathogenic

Sep 2016 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.2830A>T (p.Lys944Ter)

Variation ID: 51355 Accession: VCV000051355.51

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 13q13.1 13: 32337185 (GRCh38) [ NCBI UCSC ] 13: 32911322 (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	Nov 24, 2024	Sep 8, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_000059.4:c.2830A>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000050.3:p.Lys944Ter	nonsense
NC_000013.11:g.32337185A>T
NC_000013.10:g.32911322A>T
NG_012772.3:g.26706A>T
LRG_293:g.26706A>T
LRG_293t1:c.2830A>T	LRG_293p1:p.Lys944Ter
U43746.1:n.3058A>T

... more HGVS ... less HGVS

Protein change

K944*

Other names

p.K944*:AAA>TAA
3058A>T

Canonical SPDI

NC_000013.11:32337184:A:T

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.

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

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

Links

ClinGen: CA016531 dbSNP: rs80358533 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.
Familial cancer of breast	Pathogenic (1)	criteria provided, single submitter	Mar 25, 2024	RCV000044070.13
Breast-ovarian cancer, familial, susceptibility to, 2	Pathogenic (13)	reviewed by expert panel	Sep 8, 2016	RCV000077287.27
Hereditary cancer-predisposing syndrome	Pathogenic (3)	criteria provided, multiple submitters, no conflicts	Jul 20, 2023	RCV000131101.21
not provided	Pathogenic (9)	criteria provided, multiple submitters, no conflicts	Sep 15, 2024	RCV000212222.31
Hereditary breast ovarian cancer syndrome	Pathogenic (7)	criteria provided, multiple submitters, no conflicts	Jan 12, 2024	RCV000496649.20
Ovarian neoplasm	Pathogenic (1)	no assertion criteria provided	Dec 1, 2018	RCV000785217.10
Fanconi anemia complementation group D1	Pathogenic (1)	no assertion criteria provided	Feb 5, 2020	RCV001028039.9
Malignant tumor of breast	Pathogenic (1)	no assertion criteria provided	-	RCV001358552.10
BRCA2-related disorder	Pathogenic (1)	no assertion criteria provided	Aug 20, 2024	RCV004724777.1

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.
Pathogenic (Sep 08, 2016)	reviewed by expert panel (ENIGMA BRCA1/2 Classification Criteria (2015)) 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: SCV000300563.2 First in ClinVar: Sep 24, 2016 Last updated: Sep 24, 2016	Comment: Variant allele predicted to encode a truncated non-functional protein.
Pathogenic (Nov 07, 2017)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics and Genomics, Karolinska University Hospital Accession: SCV001450006.1 First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020	Number of individuals with the variant: 1
Pathogenic (Jun 19, 2021)	criteria provided, single submitter (Sema4 Curation Guidelines) Method: curation	Hereditary cancer-predisposing syndrome Affected status: unknown Allele origin: germline	Sema4, Sema4 Accession: SCV002535532.1 First in ClinVar: Jun 24, 2022 Last updated: Jun 24, 2022 Comment: The BRCA2 c.2830A>T (p.K944) variant has been reported in heterozygosity in numerous individuals with breast and ovarian cancer (PMID: 9150154, 28993434, 23940062, 22535016, 27767231). This … (more) The BRCA2 c.2830A>T (p.K944) variant has been reported in heterozygosity in numerous individuals with breast and ovarian cancer (PMID: 9150154, 28993434, 23940062, 22535016, 27767231). This nonsense variant creates a premature stop codon at residue 944 of the BRCA2 protein. Loss of function variants in BRCA1 or BRCA2 are known to be pathogenic (PMID: 29446198). This variant was observed in 1/24868 chromosomes in the African/African American population according to the Genome Aggregation Database (http://gnomad.broadinstitute.org, PMID: 32461654). This variant has been reported in ClinVar (Variation ID: 51355). Based on the current evidence available, this variant is interpreted as pathogenic. (less)	Publications: PubMed (6) PubMed: 9150154‚ 28993434‚ 23940062‚ 22535016‚ 27767231‚ 29446198
Pathogenic (Oct 02, 2015)	criteria provided, single submitter (CIMBA Mutation Classification guidelines May 2016) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: unknown Allele origin: germline	Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge Accession: SCV000326771.4 First in ClinVar: Nov 05, 2016 Last updated: Dec 11, 2022
Pathogenic (Jul 01, 2015)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Department of Medical Genetics, Oslo University Hospital Accession: SCV000605671.3 First in ClinVar: Sep 30, 2017 Last updated: Dec 11, 2022	Number of individuals with the variant: 8
Pathogenic (Jul 02, 2018)	criteria provided, single submitter (Mendelics Assertion Criteria 2017) Method: clinical testing	Hereditary breast and ovarian cancer syndrome Affected status: unknown Allele origin: unknown	Mendelics Accession: SCV000838779.2 First in ClinVar: Oct 10, 2018 Last updated: Dec 11, 2022
Pathogenic (Sep 30, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Revvity Omics, Revvity Accession: SCV002021563.3 First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024
Pathogenic (May 27, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet Accession: SCV005045992.1 First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024	Comment: PVS1; PM5_PTC_Strong
Pathogenic (Mar 25, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Familial cancer of breast Affected status: unknown Allele origin: unknown	Baylor Genetics Accession: SCV000540994.2 First in ClinVar: May 29, 2016 Last updated: Jun 17, 2024
Pathogenic (Jul 31, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV002550312.6 First in ClinVar: Jul 30, 2022 Last updated: Aug 04, 2024
Pathogenic (Jun 20, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics Laboratory, Skane University Hospital Lund Accession: SCV005199780.1 First in ClinVar: Aug 25, 2024 Last updated: Aug 25, 2024
Pathogenic (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: SCV000744431.1 First in ClinVar: Apr 19, 2018 Last updated: Apr 19, 2018
Pathogenic (Jan 30, 2021)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000694634.2 First in ClinVar: Aug 07, 2017 Last updated: Feb 13, 2021	Publications: PubMed (1) PubMed: 29446198 Comment: Variant summary: BRCA2 c.2830A>T (p.Lys944X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more) Variant summary: BRCA2 c.2830A>T (p.Lys944X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250612 control chromosomes. c.2830A>T has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Multiple clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. (less)
Pathogenic (Feb 01, 2022)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: research	Hereditary breast ovarian cancer syndrome Affected status: yes Allele origin: germline	Research Institute, Aichi Cancer Center Accession: SCV002503891.1 First in ClinVar: Apr 30, 2022 Last updated: Apr 30, 2022	Number of individuals with the variant: 1 Sex: female Ethnicity/Population group: East asian
Pathogenic (Aug 11, 2015)	criteria provided, single submitter (Counsyl Autosomal Dominant Disease Classification criteria (2015)) Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: unknown Allele origin: unknown	Counsyl Accession: SCV000677672.2 First in ClinVar: Jan 06, 2018 Last updated: Dec 24, 2022	Publications: PubMed (3) PubMed: 9150154‚ 20104584‚ 22535016
Pathogenic (Jan 06, 2021)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000210293.15 First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023	Comment: Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not … (more) Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 25525159, 26659639, 20104584, 23683081, 26064523, 25428789, 9150154, 16760289, 23940062, 22535016, 11430722, 20608899, 10359546, 16847550, 14732925, 24737347, 9892109, 18465347, 11710835, 27767231, 27836010, 28127413, 26681312, 29339979, 28993434, 29506128, 29446198, 30720243, 30702160, 30322717, 31589614, 32885271, 33087929, 33287145) (less)
Pathogenic (Nov 26, 2019)	criteria provided, single submitter (Quest Diagnostics criteria) Method: clinical testing	not provided Affected status: unknown Allele origin: unknown	Quest Diagnostics Nichols Institute San Juan Capistrano Accession: SCV000296716.4 First in ClinVar: Sep 27, 2014 Last updated: Jan 06, 2024	Publications: PubMed (24) PubMed: 26295337‚ 20608899‚ 22535016‚ 25525159‚ 28993434‚ 29339979‚ 29446198‚ 30322717‚ 30702160‚ 30720243‚ 31263571‚ 31589614‚ 32091409‚ 32885271‚ 33087929‚ 33287145‚ 9150154‚ 26681312‚ 27767231‚ 29506128‚ 23940062‚ 23683081‚ 16760289‚ 20104584 Comment: This nonsense variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in a number of individuals with breast and … (more) This nonsense variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in a number of individuals with breast and ovarian cancers (PMID: 27767231 (2017), 26681312 (2015), 23940062 (2013), 23683081 (2013), 20104584 (2010), 16760289 (2006), 9150154 (1997)) and in one case of pancreatic cancer (PMID: 29506128 (2018)). Based on the available information, this variant is classified as pathogenic. (less)
Pathogenic (Jul 20, 2023)	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: SCV000292148.4 First in ClinVar: Jul 08, 2016 Last updated: Feb 14, 2024	Publications: PubMed (12) PubMed: 18284688‚ 18465347‚ 19574032‚ 20104584‚ 22535016‚ 23096105‚ 23683081‚ 29446198‚ 30322717‚ 32885271‚ 34072659‚ 34309133 Comment: This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in … (more) This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals with a personal and/or family history of breast, ovarian, or pancreatic cancer (PMID: 18465347, 18284688, 19574032, 20104584, 22535016, 23096105, 23683081, 29446198, 30322717, 32885271, 34072659. 34309133). This variant has been identified in 3/282020 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less)
Pathogenic (Jan 12, 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: SCV001588423.4 First in ClinVar: May 10, 2021 Last updated: Feb 20, 2024	Publications: PubMed (5) PubMed: 20104584‚ 9150154‚ 23683081‚ 26681312‚ 27836010 Comment: This sequence change creates a premature translational stop signal (p.Lys944) in the BRCA2 gene. It is expected to result in an absent or disrupted protein … (more) This sequence change creates a premature translational stop signal (p.Lys944) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80358533, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 9150154, 20104584, 23683081, 26681312, 27836010). This variant is also known as 3058A>T. ClinVar contains an entry for this variant (Variation ID: 51355). For these reasons, this variant has been classified as Pathogenic. (less)
Pathogenic (Jan 06, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) 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: SCV004845066.1 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)	Publications: PubMed (11) PubMed: 18284688‚ 18465347‚ 19574032‚ 20104584‚ 22535016‚ 23096105‚ 23683081‚ 29446198‚ 30322717‚ 32885271‚ 34072659 Comment: This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in … (more) This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals with a personal and/or family history of breast, ovarian, or pancreatic cancer (PMID: 18465347, 18284688, 19574032, 20104584, 22535016, 23096105, 23683081, 29446198, 30322717, 32885271, 34072659. 34309133). This variant has been identified in 3/282020 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. (less) Number of individuals with the variant: 2
Pathogenic (Oct 14, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Hereditary breast ovarian cancer syndrome Affected status: unknown Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV004848271.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024	Publications: PubMed (8) PubMed: 9150154‚ 20608899‚ 22535016‚ 23940062‚ 26681312‚ 27767231‚ 29506128‚ 28993434 Comment: The p.Lys944X variant in BRCA2 has been reported in at least 11 individuals with BRCA2-related cancers; however two of these individuals harbored pathogenic variants in … (more) The p.Lys944X variant in BRCA2 has been reported in at least 11 individuals with BRCA2-related cancers; however two of these individuals harbored pathogenic variants in BRCA1 as well (Hakansson 1997, Heidemann 2012, Vietri 2013, Susswein 2016, Weren 2017, Lowery 2018, Wen 2018, BIC database). In addition, this variant was reported in one proband with Fanconi anemia who was compound heterozygous for this variant and a second variant in BRCA2 (Bodd 2010). The p.Lys944X variant has also been identified in 0.004% (1/24868) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This nonsense variant is predicted to lead to a premature termination codon at position 944. Loss of function of the BRCA2 gene is an established disease mechanism in autosomal dominant HBOC. Additionally, this variant was classified as Pathogenic on Sep 8, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID: 51355). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PS4_Moderate, PP1. (less)
Pathogenic (Oct 01, 2021)	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: SCV000186031.8 First in ClinVar: Aug 06, 2014 Last updated: May 01, 2024	Publications: PubMed (19) PubMed: 14732925‚ 16760289‚ 18465347‚ 20608899‚ 22535016‚ 23940062‚ 24737347‚ 26681312‚ 27767231‚ 27836010‚ 28993434‚ 29339979‚ 29446198‚ 29506128‚ 30322717‚ 32091409‚ 32885271‚ 33471991‚ 34309133 Comment: The p.K944* pathogenic mutation (also known as c.2830A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at … (more) The p.K944* pathogenic mutation (also known as c.2830A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 2830. This changes the amino acid from a lysine to a stop codon within coding exon 10. This mutation has been detected in multiple breast and ovarian cancer families to date (Mote PA et al. Genes Chromosomes Cancer, 2004 Mar;39:236-48; Capalbo C et al. Ann Oncol, 2006 Jun;17 Suppl 7:vii34-40; Thomassen M et al. Acta Oncol, 2008;47:772-7; Bodd TL et al. Acta Paediatr., 2010 Nov;99:1741-3; Heidemann S et al. Breast Cancer Res Treat, 2012 Aug;134:1229-39; Vietri MT et al. Clin. Chem. Lab. Med., 2013 Dec;51:2319-24; Lucas AL et al. Cancer, 2014 Jul;120:1960-7; Rebbeck TR et al. Breast Cancer Res, 2016 11;18:112; Susswein LR et al. Genet Med, 2016 08;18:823-32; Weren RD et al. Hum. Mutat., 2017 02;38:226-235; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Wen WX et al. J Med Genet, 2018 02;55:97-103; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Chen B et al. Aging (Albany NY), 2020 02;12:3140-3155; Lerner-Ellis J et al. J Cancer Res Clin Oncol, 2021 Mar;147:871-879). In one study, this variant was reported in 2/60,466 breast cancer cases and in 2/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This mutation has also been reported in patients with pancreatic cancer (Lowery MA et al. J Natl Cancer Inst, 2018 10;110:1067-1074; Sorscher S et al. Oncologist, 2021 Jul). Of note, this alteration is also designated as 3058A>T in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. (less)
Pathogenic (Jan 30, 2019)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	hereditary breast and ovarian cancer syndrome Affected status: unknown Allele origin: unknown	Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine Accession: SCV005045768.1 First in ClinVar: Jun 02, 2024 Last updated: Jun 02, 2024	Comment: The c.2830A>T (p.Lys944) variant of BRCA2 results in an early stop codon at amino acid 944, resulting in an absent or disrupted protein product. Loss … (more) The c.2830A>T (p.Lys944) variant of BRCA2 results in an early stop codon at amino acid 944, resulting in an absent or disrupted protein product. Loss of function variants of BRCA2 are known to be pathogenic. The variant has been reported in several individuals and families with breast and/or ovarian cancer and pancreatic cancer (PMID: 29506128, 29446198, 29339979, 28346442, 27836010, 27767231, 26681312, 24737347, 23940062, 23683081, 22535016, 20104584, 18465347, 16760289, 10359546 and 9150154). This variant is observed in the population database at very low frequency (3/282020). Based on the currently available information, the c.2830A>T (p.Lys944*) variant of BRCA2 is classified as pathogenic. (less)
Pathogenic (May 01, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not provided Affected status: no Allele origin: inherited	Centre for Clinical Genetics and Genomic Diagnostics, Zealand University Hospital Accession: SCV005328476.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024
Pathogenic (Sep 15, 2024)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Not provided Affected status: unknown Allele origin: germline	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV005414145.1 First in ClinVar: Nov 24, 2024 Last updated: Nov 24, 2024	Publications: PubMed (13) PubMed: 20608899‚ 26681312‚ 28993434‚ 29053726‚ 29506128‚ 29922827‚ 30322717‚ 32091409‚ 33287145‚ 35741847‚ 36292577‚ 36721989‚ 9150154 Comment: PM3, PM5_strong, PVS1 Number of individuals with the variant: 1
Pathogenic (Nov 27, 2006)	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: SCV000109084.2 First in ClinVar: Dec 23, 2013 Last updated: Sep 27, 2014
Pathogenic (Jan 31, 2014)	no assertion criteria provided Method: research	Hereditary breast ovarian cancer syndrome Affected status: yes Allele origin: germline	Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto Study: The Canadian Open Genetics Repository (COGR) Accession: SCV000587645.1 First in ClinVar: Aug 07, 2017 Last updated: Aug 07, 2017
Pathogenic (-)	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: SCV000733241.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Pathogenic (Mar 10, 2020)	no assertion criteria provided Method: clinical testing	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: no Allele origin: germline	New York Genome Center Accession: SCV001431059.2 First in ClinVar: Sep 05, 2020 Last updated: Sep 05, 2020	Publications: PubMed (4) PubMed: 24737347‚ 23683081‚ 20104584‚ 28346442 Comment: The c.2830A>T (p.Lys944Ter) variant identified in the BRCA2 gene of this individual leads to the premature termination of the protein at amino acid 944/3419 (coding … (more) The c.2830A>T (p.Lys944Ter) variant identified in the BRCA2 gene of this individual leads to the premature termination of the protein at amino acid 944/3419 (coding exon 11/27). This variant is found with low frequency in gnomAD (3 heterozygotes, 0 homozygotes, allele frequency: 1.06e-5) suggesting it is not a common benign variant in the populations represented in these databases. This variant is reported as Pathogenic in ClinVar (VarID:51355) after review by the Expert Panel and has been reported in many affected individuals in the literature [PMID: 24737347; PMID: 23683081; PMID: 20104584; PMID: 28346442]. It is reported here as Pathogenic. (less) Secondary finding: yes Method: whole genome sequencing
Pathogenic (-)	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: SCV001554320.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021	Comment: The BRCA2 p.Lys944X variant was identified in 8 of 25752 proband chromosomes (frequency: 0.0003) from individuals or families with breast and ovarian cancer (Blay 2013, … (more) The BRCA2 p.Lys944X variant was identified in 8 of 25752 proband chromosomes (frequency: 0.0003) from individuals or families with breast and ovarian cancer (Blay 2013, Borg 2010, Capalbo 2006, Hakansson 1997, Heramb 2018, Susswein 2015). The variant was also identified in the following databases: dbSNP (ID: rs80358533) as "With Pathogenic allele", ClinVar (12x pathogenic), Clinvitae (5x pathogenic), GeneInsight-COGR (2x pathogenic), Cosmic (1x, confirmed somatic, in carcinoma of the biliary tract), LOVD 3.0 (11x), UMD-LSDB (8x causal), BIC Database (6x pathogenic), and ARUP Laboratories (pathogenic). The variant was not identified in MutDB or the Zhejiang Colon Cancer Database. The variant was identified in control databases in 3 of 276604 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 23994 chromosomes (freq: 0.00004), European in 1 of 126388 chromosomes (freq: 0.000008), and South Asian in 1 of 30678 chromosomes (freq: 0.00003). The variant was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, or Finnish populations. The c.2830A>T variant leads to a premature stop codon at position 944 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic. (less) Number of individuals with the variant: 2
Pathogenic (Aug 20, 2024)	no assertion criteria provided Method: clinical testing	BRCA2-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV005337059.1 First in ClinVar: Oct 08, 2024 Last updated: Oct 08, 2024	Comment: The BRCA2 c.2830A>T variant is predicted to result in premature protein termination (p.Lys944). This variant has been reported in multiple individuals with breast and/or ovarian … (more) The BRCA2 c.2830A>T variant is predicted to result in premature protein termination (p.Lys944). This variant has been reported in multiple individuals with breast and/or ovarian cancer (Table 2, Hakansson et al. 1997. PubMed ID: 9150154; Figure 1, Heidemann et al. 2012. PubMed ID: 22535016; Table 1, Weren et al. 2016. PubMed ID: 27767231). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD and it has been classified as pathogenic by an expert panel in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/51355/). Nonsense variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic. (less)
Pathogenic (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: SCV000146122.1 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: 1 Geographic origin: Denmark Observation 3: Number of individuals with the variant: 1 Ethnicity/Population group: African American Observation 4: Number of individuals with the variant: 1 Ethnicity/Population group: Western European
Pathogenic (Dec 01, 2018)	no assertion criteria provided Method: research	Ovarian neoplasm Affected status: yes Allele origin: germline	German Consortium for Hereditary Breast and Ovarian Cancer, University Hospital Cologne Accession: SCV000923785.1 First in ClinVar: Jun 17, 2019 Last updated: Jun 17, 2019
Pathogenic (Feb 05, 2020)	no assertion criteria provided Method: clinical testing	Fanconi anemia complementation group D1 Affected status: yes Allele origin: germline	Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City Accession: SCV001190805.1 First in ClinVar: Mar 29, 2020 Last updated: Mar 29, 2020
Pathogenic (-)	no assertion criteria provided Method: clinical testing	not provided 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: SCV001954387.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Pathogenic (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: SCV004243595.1 First in ClinVar: Feb 14, 2024 Last updated: Feb 14, 2024
Pathogenic (May 24, 2021)	no assertion criteria provided Method: case-control	Breast-ovarian cancer, familial, susceptibility to, 2 Affected status: yes Allele origin: germline	Molecular Oncology, Hospital Universitario Central de Asturias (HUCA) Accession: SCV005061319.1 First in ClinVar: Oct 13, 2024 Last updated: Oct 13, 2024	Publications: PubMed (1) PubMed: 38922859 Secondary finding: no
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Comment:

Variant summary: BRCA2 c.2830A>T (p.Lys944X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 8e-06 in 250612 control chromosomes. c.2830A>T has been reported in the literature in multiple individuals affected with Hereditary Breast And Ovarian Cancer Syndrome (example, Rebbeck_2018). These data indicate that the variant is very likely to be associated with disease. Multiple clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

Comment:

Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; This variant is associated with the following publications: (PMID: 25525159, 26659639, 20104584, 23683081, 26064523, 25428789, 9150154, 16760289, 23940062, 22535016, 11430722, 20608899, 10359546, 16847550, 14732925, 24737347, 9892109, 18465347, 11710835, 27767231, 27836010, 28127413, 26681312, 29339979, 28993434, 29506128, 29446198, 30720243, 30702160, 30322717, 31589614, 32885271, 33087929, 33287145)

Comment:

This nonsense variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in a number of individuals with breast and ovarian cancers (PMID: 27767231 (2017), 26681312 (2015), 23940062 (2013), 23683081 (2013), 20104584 (2010), 16760289 (2006), 9150154 (1997)) and in one case of pancreatic cancer (PMID: 29506128 (2018)). Based on the available information, this variant is classified as pathogenic.

Comment:

This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals with a personal and/or family history of breast, ovarian, or pancreatic cancer (PMID: 18465347, 18284688, 19574032, 20104584, 22535016, 23096105, 23683081, 29446198, 30322717, 32885271, 34072659. 34309133). This variant has been identified in 3/282020 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

Comment:

This sequence change creates a premature translational stop signal (p.Lys944*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant is present in population databases (rs80358533, gnomAD 0.004%). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 9150154, 20104584, 23683081, 26681312, 27836010). This variant is also known as 3058A>T. ClinVar contains an entry for this variant (Variation ID: 51355). For these reasons, this variant has been classified as Pathogenic.

Comment:

The p.Lys944X variant in BRCA2 has been reported in at least 11 individuals with BRCA2-related cancers; however two of these individuals harbored pathogenic variants in BRCA1 as well (Hakansson 1997, Heidemann 2012, Vietri 2013, Susswein 2016, Weren 2017, Lowery 2018, Wen 2018, BIC database). In addition, this variant was reported in one proband with Fanconi anemia who was compound heterozygous for this variant and a second variant in BRCA2 (Bodd 2010). The p.Lys944X variant has also been identified in 0.004% (1/24868) of African chromosomes by gnomAD (http://gnomad.broadinstitute.org); however, this frequency is low enough to be consistent with the frequency of hereditary breast and ovarian cancer (HBOC) in the general population. This nonsense variant is predicted to lead to a premature termination codon at position 944. Loss of function of the BRCA2 gene is an established disease mechanism in autosomal dominant HBOC. Additionally, this variant was classified as Pathogenic on Sep 8, 2016 by the ClinGen-approved ENIGMA expert panel (Variation ID: 51355). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant HBOC. ACMG/AMP Criteria applied: PVS1, PS4_Moderate, PP1.

Comment:

The p.K944* pathogenic mutation (also known as c.2830A>T), located in coding exon 10 of the BRCA2 gene, results from an A to T substitution at nucleotide position 2830. This changes the amino acid from a lysine to a stop codon within coding exon 10. This mutation has been detected in multiple breast and ovarian cancer families to date (Mote PA et al. Genes Chromosomes Cancer, 2004 Mar;39:236-48; Capalbo C et al. Ann Oncol, 2006 Jun;17 Suppl 7:vii34-40; Thomassen M et al. Acta Oncol, 2008;47:772-7; Bodd TL et al. Acta Paediatr., 2010 Nov;99:1741-3; Heidemann S et al. Breast Cancer Res Treat, 2012 Aug;134:1229-39; Vietri MT et al. Clin. Chem. Lab. Med., 2013 Dec;51:2319-24; Lucas AL et al. Cancer, 2014 Jul;120:1960-7; Rebbeck TR et al. Breast Cancer Res, 2016 11;18:112; Susswein LR et al. Genet Med, 2016 08;18:823-32; Weren RD et al. Hum. Mutat., 2017 02;38:226-235; Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3; Wen WX et al. J Med Genet, 2018 02;55:97-103; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Carter NJ et al. Gynecol Oncol, 2018 12;151:481-488; Chen B et al. Aging (Albany NY), 2020 02;12:3140-3155; Lerner-Ellis J et al. J Cancer Res Clin Oncol, 2021 Mar;147:871-879). In one study, this variant was reported in 2/60,466 breast cancer cases and in 2/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This mutation has also been reported in patients with pancreatic cancer (Lowery MA et al. J Natl Cancer Inst, 2018 10;110:1067-1074; Sorscher S et al. Oncologist, 2021 Jul). Of note, this alteration is also designated as 3058A>T in the literature. In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

Comment:

The c.2830A>T (p.Lys944*) variant of BRCA2 results in an early stop codon at amino acid 944, resulting in an absent or disrupted protein product. Loss of function variants of BRCA2 are known to be pathogenic. The variant has been reported in several individuals and families with breast and/or ovarian cancer and pancreatic cancer (PMID: 29506128, 29446198, 29339979, 28346442, 27836010, 27767231, 26681312, 24737347, 23940062, 23683081, 22535016, 20104584, 18465347, 16760289, 10359546 and 9150154). This variant is observed in the population database at very low frequency (3/282020). Based on the currently available information, the c.2830A>T (p.Lys944*) variant of BRCA2 is classified as pathogenic.

Comment:

The c.2830A>T (p.Lys944Ter) variant identified in the BRCA2 gene of this individual leads to the premature termination of the protein at amino acid 944/3419 (coding exon 11/27). This variant is found with low frequency in gnomAD (3 heterozygotes, 0 homozygotes, allele frequency: 1.06e-5) suggesting it is not a common benign variant in the populations represented in these databases. This variant is reported as Pathogenic in ClinVar (VarID:51355) after review by the Expert Panel and has been reported in many affected individuals in the literature [PMID: 24737347; PMID: 23683081; PMID: 20104584; PMID: 28346442]. It is reported here as Pathogenic.

Comment:

The BRCA2 p.Lys944X variant was identified in 8 of 25752 proband chromosomes (frequency: 0.0003) from individuals or families with breast and ovarian cancer (Blay 2013, Borg 2010, Capalbo 2006, Hakansson 1997, Heramb 2018, Susswein 2015). The variant was also identified in the following databases: dbSNP (ID: rs80358533) as "With Pathogenic allele", ClinVar (12x pathogenic), Clinvitae (5x pathogenic), GeneInsight-COGR (2x pathogenic), Cosmic (1x, confirmed somatic, in carcinoma of the biliary tract), LOVD 3.0 (11x), UMD-LSDB (8x causal), BIC Database (6x pathogenic), and ARUP Laboratories (pathogenic). The variant was not identified in MutDB or the Zhejiang Colon Cancer Database. The variant was identified in control databases in 3 of 276604 chromosomes at a frequency of 0.00001 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 1 of 23994 chromosomes (freq: 0.00004), European in 1 of 126388 chromosomes (freq: 0.000008), and South Asian in 1 of 30678 chromosomes (freq: 0.00003). The variant was not observed in the Other, Latino, Ashkenazi Jewish, East Asian, or Finnish populations. The c.2830A>T variant leads to a premature stop codon at position 944 which is predicted to lead to a truncated or absent protein and loss of function. Loss of function variants of the BRCA2 gene are an established mechanism of disease in hereditary breast and ovarian cancer and is the type of variant expected to cause the disorder. In summary, based on the above information this variant meets our laboratoryâ€šÃ„Ã´s criteria to be classified as pathogenic.

Comment:

The BRCA2 c.2830A>T variant is predicted to result in premature protein termination (p.Lys944*). This variant has been reported in multiple individuals with breast and/or ovarian cancer (Table 2, Hakansson et al. 1997. PubMed ID: 9150154; Figure 1, Heidemann et al. 2012. PubMed ID: 22535016; Table 1, Weren et al. 2016. PubMed ID: 27767231). This variant is reported in 0.0040% of alleles in individuals of African descent in gnomAD and it has been classified as pathogenic by an expert panel in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/51355/). Nonsense variants in BRCA2 are expected to be pathogenic. This variant is interpreted as pathogenic.

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
Featuring BRCA1 and BRCA2 germline mutational landscape from Asturias (North Spain).	Pitiot AS	Clinical genetics	2024	PMID: 38922859
A novel cancer risk prediction score for the natural course of FA patients with biallelic BRCA2/FANCD1 mutations.	Radulovic I	Human molecular genetics	2023	PMID: 36721989
Increased Risk of Hereditary Prostate Cancer in Italian Families with Hereditary Breast and Ovarian Cancer Syndrome Harboring Mutations in BRCA and in Other Susceptibility Genes.	D'Elia G	Genes	2022	PMID: 36292577
Prevalence of Pathogenic Germline BRCA1/2 Variants and Their Association with Clinical Characteristics in Patients with Epithelial Ovarian Cancer in a Rural Area of Japan.	Abe A	Genes	2022	PMID: 35741847
Rapid Progression of Metastatic Pancreatic Adenocarcinoma During Platinum-Based Therapy in a Patient Harboring a Pathogenic BRCA2 Germline Variant.	Sorscher S	The oncologist	2021	PMID: 34309133
Study of the Genetic Variants in BRCA1/2 and Non-BRCA Genes in a Population-Based Cohort of 2155 Breast/Ovary Cancer Patients, Including 443 Triple-Negative Breast Cancer Patients, in Argentina.	Solano AR	Cancers	2021	PMID: 34072659
Breast Cancer Risk Genes - Association Analysis in More than 113,000 Women.	Breast Cancer Association Consortium	The New England journal of medicine	2021	PMID: 33471991
Multigene panel testing for hereditary breast and ovarian cancer in the province of Ontario.	Lerner-Ellis J	Journal of cancer research and clinical oncology	2021	PMID: 32885271
Five Italian Families with Two Mutations in BRCA Genes.	Vietri MT	Genes	2020	PMID: 33287145
Exome sequencing and characterization of 49,960 individuals in the UK Biobank.	Van Hout CV	Nature	2020	PMID: 33087929
Comparison of BRCA versus non-BRCA germline mutations and associated somatic mutation profiles in patients with unselected breast cancer.	Chen B	Aging	2020	PMID: 32091409
Optimizing clinical exome design and parallel gene-testing for recessive genetic conditions in preconception carrier screening: Translational research genomic data from 14,125 exomes.	Capalbo A	PLoS genetics	2019	PMID: 31589614
High frequency of pathogenic germline variants within homologous recombination repair in patients with advanced cancer.	Bertelsen B	NPJ genomic medicine	2019	PMID: 31263571
High prevalence of cancer-associated TP53 variants in the gnomAD database: A word of caution concerning the use of variant filtering.	Soussi T	Human mutation	2019	PMID: 30720243
Germline variation in BRCA1/2 is highly ethnic-specific: Evidence from over 30,000 Chinese hereditary breast and ovarian cancer patients.	Bhaskaran SP	International journal of cancer	2019	PMID: 30702160
Germline pathogenic variants identified in women with ovarian tumors.	Carter NJ	Gynecologic oncology	2018	PMID: 30322717
Association Between Inherited Germline Mutations in Cancer Predisposition Genes and Risk of Pancreatic Cancer.	Hu C	JAMA	2018	PMID: 29922827
Prospective Evaluation of Germline Alterations in Patients With Exocrine Pancreatic Neoplasms.	Lowery MA	Journal of the National Cancer Institute	2018	PMID: 29506128
Mutational spectrum in a worldwide study of 29,700 families with BRCA1 or BRCA2 mutations.	Rebbeck TR	Human mutation	2018	PMID: 29446198
BRCA1 and BRCA2 mutation spectrum - an update on mutation distribution in a large cancer genetics clinic in Norway.	Heramb C	Hereditary cancer in clinical practice	2018	PMID: 29339979
Inherited mutations in BRCA1 and BRCA2 in an unselected multiethnic cohort of Asian patients with breast cancer and healthy controls from Malaysia.	Wen WX	Journal of medical genetics	2018	PMID: 28993434
Prevalence of deleterious germline variants in risk genes including BRCA1/2 in consecutive ovarian cancer patients (AGO-TR-1).	Harter P	PloS one	2017	PMID: 29053726
Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.	Phelan CM	Nature genetics	2017	PMID: 28346442
Novel BRCA1 and BRCA2 Tumor Test as Basis for Treatment Decisions and Referral for Genetic Counselling of Patients with Ovarian Carcinomas.	Weren RD	Human mutation	2017	PMID: 27767231
Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women.	Rebbeck TR	Breast cancer research : BCR	2016	PMID: 27836010
Pathogenic and likely pathogenic variant prevalence among the first 10,000 patients referred for next-generation cancer panel testing.	Susswein LR	Genetics in medicine : official journal of the American College of Medical Genetics	2016	PMID: 26681312
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease.	Xiong HY	Science (New York, N.Y.)	2015	PMID: 25525159
BRCA1 and BRCA2 germline mutations are frequently demonstrated in both high-risk pancreatic cancer screening and pancreatic cancer cohorts.	Lucas AL	Cancer	2014	PMID: 24737347
Double heterozygosity in the BRCA1 and BRCA2 genes in Italian family.	Vietri MT	Clinical chemistry and laboratory medicine	2013	PMID: 23940062
Mutational analysis of BRCA1 and BRCA2 in hereditary breast and ovarian cancer families from Asturias (Northern Spain).	Blay P	BMC cancer	2013	PMID: 23683081
Identification of a novel in-frame deletion in BRCA2 and analysis of variants of BRCA1/2 in Italian patients affected with hereditary breast and ovarian cancer.	Vietri MT	Clinical chemistry and laboratory medicine	2012	PMID: 23096105
Double heterozygosity for mutations in BRCA1 and BRCA2 in German breast cancer patients: implications on test strategies and clinical management.	Heidemann S	Breast cancer research and treatment	2012	PMID: 22535016
Fanconi anaemia, BRCA2 and familial considerations - follow up on a previous case report.	Bodd TL	Acta paediatrica (Oslo, Norway : 1992)	2010	PMID: 20608899
Characterization of BRCA1 and BRCA2 deleterious mutations and variants of unknown clinical significance in unilateral and bilateral breast cancer: the WECARE study.	Borg A	Human mutation	2010	PMID: 20104584
Dramatic response to platinum in a patient with cancer with a germline BRCA2 mutation.	Moule R	Clinical oncology (Royal College of Radiologists (Great Britain))	2009	PMID: 19574032
BRCA1 and BRCA2 mutations in Danish families with hereditary breast and/or ovarian cancer.	Thomassen M	Acta oncologica (Stockholm, Sweden)	2008	PMID: 18465347
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
BRCA1 and BRCA2 genetic testing in Italian breast and/or ovarian cancer families: mutation spectrum and prevalence and analysis of mutation prediction models.	Capalbo C	Annals of oncology : official journal of the European Society for Medical Oncology	2006	PMID: 16760289
Germ-line mutations in BRCA1 or BRCA2 in the normal breast are associated with altered expression of estrogen-responsive proteins and the predominance of progesterone receptor A.	Mote PA	Genes, chromosomes & cancer	2004	PMID: 14732925
Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer.	Håkansson S	American journal of human genetics	1997	PMID: 9150154
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Text-mined citations for rs80358533 ...

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.2830A>T (p.Lys944Ter)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs80358533 ...