Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000045026 | SCV000073039 | likely benign | Hereditary breast and ovarian cancer syndrome | 2019-12-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000165940 | SCV000216696 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-12-12 | criteria provided, single submitter | clinical testing | The p.E2236K variant (also known as c.6706G>A), located in coding exon 10 of the BRCA2 gene, results from a G to A substitution at nucleotide position 6706. The glutamic acid at codon 2236 is replaced by lysine, an amino acid with similar properties. This alteration has been identified in several European cohorts of breast, ovarian and prostate cancer patients (Kote-Jarai Z et al. Br. J. Cancer, 2011 Oct;105:1230-4; Moghadasi S et al. J. Med. Genet., 2013 Feb;50:74-9; Kluska A et al. BMC Med Genomics, 2015 May;8:19; Cunningham JM et al. Sci Rep, 2014 Feb;4:4026). This alteration was detected in trans with a pathogenic BRCA2 mutation in an individual who did not have a personal or family history that is consistent with or suggestive of Fanconi Anemia (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is conflicting at this time, the clinical significance of this alteration remains unclear. |
Gene |
RCV000216299 | SCV000278872 | uncertain significance | not provided | 2018-11-08 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.6706G>A at the cDNA level, p.Glu2236Lys (E2236K) at the protein level, and results in the change of a Glutamic Acid to a Lysine (GAA>AAA). Using alternate nomenclature, this variant would be defined as BRCA2 6934G>A. This variant has been observed in individuals with personal and/or family histories of breast and/or ovarian cancer and in at least one individual with early-onset prostate cancer (Kote-Jarai 2011, Moghadasi 2013, Cunningham 2014, Kluska 2015, Lincoln 2015). BRCA2 Glu2236Lys was not observed at a significant allele frequency in large population cohorts (Lek 2016). BRCA2 Glu2236Lys is not located in a known functional domain. In silico analysis, which includes protein predictors?and evolutionary conservation, support a deleterious effect. Based on currently available evidence, it is unclear whether BRCA2 Glu2236Lys is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. |
Color Health, |
RCV000165940 | SCV000683802 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-03-27 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000083129 | SCV000785196 | uncertain significance | Breast-ovarian cancer, familial 2 | 2017-05-31 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000763895 | SCV000894830 | uncertain significance | Familial cancer of breast; Breast-ovarian cancer, familial 2; Fanconi anemia, complementation group D1; Medulloblastoma; Wilms tumor 1; Malignant tumor of prostate; Pancreatic cancer 2; Glioma susceptibility 3 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000781142 | SCV000919005 | uncertain significance | not specified | 2018-09-25 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6706G>A (p.Glu2236Lys) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.3e-05 in 246152 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.6706G>A has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer. However, these data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Illumina Clinical Services Laboratory, |
RCV001109885 | SCV001267263 | uncertain significance | Fanconi anemia, complementation group D1 | 2017-04-27 | 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Clinical Services Laboratory, |
RCV000083129 | SCV001267264 | uncertain significance | Breast-ovarian cancer, familial 2 | 2017-04-27 | 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Sharing Clinical Reports Project |
RCV000083129 | SCV000115203 | likely benign | Breast-ovarian cancer, familial 2 | 2012-05-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000083129 | SCV000146913 | uncertain significance | Breast-ovarian cancer, familial 2 | 2004-02-20 | no assertion criteria provided | clinical testing |