ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.2803G>A (p.Asp935Asn) (rs28897716)

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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000044061 SCV000072074 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Counsyl RCV000083092 SCV000154040 likely benign Breast-ovarian cancer, familial 2 2014-01-02 criteria provided, single submitter literature only
GeneDx RCV000120336 SCV000167347 benign not specified 2013-11-06 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000129118 SCV000183834 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000768590 SCV000219318 likely benign Breast and/or ovarian cancer 2019-04-09 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120336 SCV000225169 likely benign not specified 2014-09-10 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000083092 SCV000383659 likely benign Breast-ovarian cancer, familial 2 2018-10-17 criteria provided, single submitter clinical testing 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.
Illumina Clinical Services Laboratory,Illumina RCV000397028 SCV000383660 likely benign Fanconi anemia, complementation group D1 2018-10-17 criteria provided, single submitter clinical testing 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000120336 SCV000538472 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing 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: Multiple publications classify as VUS/not pathogenic; ExAC: 0.1% (57/66390) European chromosomes
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001282812 SCV000602765 benign none provided 2019-10-17 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129118 SCV000683501 likely benign Hereditary cancer-predisposing syndrome 2015-04-22 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000083092 SCV000743276 benign Breast-ovarian cancer, familial 2 2014-10-09 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000083092 SCV000744429 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679163 SCV000805677 likely benign not provided 2017-08-15 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000679163 SCV000892065 likely benign not provided 2021-02-01 criteria provided, single submitter clinical testing
Mendelics RCV000083092 SCV001139042 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001646105 SCV001854734 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
ITMI RCV000120336 SCV000084488 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000083092 SCV000115166 benign Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000083092 SCV000146113 benign Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353683 SCV000591825 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2, EXON11, c.2803G>A, p.Asp935Asn variant was identified in 5 of 5884 chromosomes (frequency: 0.001) from individuals with breast, ovarian or prostate cancer and was absent in 208 control chromosomes (Beetstra 2006, Capanu 2011, Edwards 2003, Soegaard 2008, Wagner 1999); however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. The variant was also identified in dbSNP (ID:rs28897716) “With non-pathogenic allele”, HGMD, LOVD, the BIC database (106X as a variant with no clinical importance), and UMD (53X as a neutral variant). In UMD, the variant was listed as co-occurring with four different pathogenic BRCA2 mutations and one pathogenic BRCA1 mutation, increasing the likelihood that this variant does not have clinical significance. In addition, Spurdle (2008) identified a homozygote with the variant who did not have clinical features of Fanconi anemia, further suggesting that this variant is neutral. In addition, the variant was listed in the 1000 Genomes Project with a frequency of 0.0005 and in the NHLBI Exome Sequencing Project with frequency of 0.0007, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The p.Asp935 residue is not conserved in mammals and computational analyses (PolyPhen2, SIFT, AlignGVGD, BLOSUM) do not suggest a high likelihood of impact to the protein. Furthermore, three in silico studies predicted the variant to have no clinical significance or effect on risk (Capanu 2011, Lindor 2012, Moghadasi 2013). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000083092 SCV000733239 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000120336 SCV001906046 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000120336 SCV001956556 benign not specified no assertion criteria provided clinical testing

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