Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000113125 | SCV001161613 | benign | Breast-ovarian cancer, familial 2 | 2019-06-18 | reviewed by expert panel | curation | 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 = 0.000661 |
Invitae | RCV000167829 | SCV000072111 | likely benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000130463 | SCV000185328 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-01 | criteria provided, single submitter | clinical testing | Co-occurence with mutation in same gene (phase unknown);In silico models in agreement (benign) |
Gene |
RCV000044098 | SCV000210584 | likely benign | not specified | 2017-10-09 | 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. |
Illumina Clinical Services Laboratory, |
RCV000113125 | SCV000383669 | uncertain significance | Breast-ovarian cancer, familial 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Clinical Services Laboratory, |
RCV000324539 | SCV000383670 | uncertain significance | Fanconi anemia, complementation group D1 | 2018-01-13 | criteria provided, single submitter | clinical testing | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Color | RCV000130463 | SCV000688782 | likely benign | Hereditary cancer-predisposing syndrome | 2016-12-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000679165 | SCV000805682 | likely benign | not provided | 2017-12-11 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000044098 | SCV000918960 | likely benign | not specified | 2019-02-27 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.2987T>G (p.Leu996Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 276496 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (4e-05 vs 0.00075). c.2987T>G has been reported in the literature once in a cohort of 493 Australian patients with triple negative breast cancer (Wong-Brown_2015). This report does not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A co-occurrence with a pathogenic variant has been reported (BRCA2 legacy name 4075delGT, c.3847_3848delGT, p.Val1283fsX2) in a patient affected with ovarian cancer with a family history significant for breast cancer in two sisters and in two nieces all of whom were positive for BRCA2 mutation (Root_2012). These data provide supporting evidence for a benign role of the variant. In addition, the variant has been reported twice in the FLOSSIES database in women older than age 70 years who have never had cancer, providing further supporting evidence for a benign role of the variant. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign (5x) and twice as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679165 | SCV001133731 | uncertain significance | not provided | 2018-11-21 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000113125 | SCV001139052 | likely benign | Breast-ovarian cancer, familial 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Breast Cancer Information Core |
RCV000113125 | SCV000146156 | uncertain significance | Breast-ovarian cancer, familial 2 | 2003-12-23 | no assertion criteria provided | clinical testing |