ClinVar Miner

Submissions for variant NM_007294.3(BRCA1):c.81-11del (rs273902788)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031280 SCV000244411 benign Breast-ovarian cancer, familial 1 2015-08-10 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 = 0.0000462
Invitae RCV001080354 SCV000259218 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
Color Health, Inc RCV000579775 SCV000683361 benign Hereditary cancer-predisposing syndrome 2017-01-03 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000587423 SCV000699305 likely benign not provided 2016-09-27 criteria provided, single submitter clinical testing Variant summary: The BRCA1 c.81-11delT variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing and an in vitro assay using RNA from the pt(s) carrying this variant shows that the variant had no effect on splicing (Menendez_2011). This variant was found in 5/104316 control chromosomes at a frequency of 0.0000479, which does not exceed the estimated maximal expected allele frequency of a pathogenic BRCA1 variant (0.0010005). This variant has been reported in affected individuals without evidence of causality. UMD cites a co-occurrence of this variant with a potentially pathogenic BRCA2 variant (c.9117+2T>C). In addition, multiple clinical diagnostic laboratories/reputable databases and publications (Lindor_2012 and Easton_2007) classified the variant as benign/likely benign. Taken together, this variant is classified as likely benign.
Mendelics RCV000031280 SCV001140649 likely benign Breast-ovarian cancer, familial 1 2019-05-28 criteria provided, single submitter clinical testing
Liquid Biopsy and Precision Medicine Group,Pfizer-University of Granada-Junta de Andalucía Centre for Genomics and Oncological Research RCV001090205 SCV001245503 uncertain significance Breast-ovarian cancer, familial 2 criteria provided, single submitter clinical testing
GeneDx RCV000587423 SCV001887701 benign not provided 2015-03-03 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 27616075, 17924331, 21990134)
Sharing Clinical Reports Project (SCRP) RCV000031280 SCV000053885 likely benign Breast-ovarian cancer, familial 1 2007-11-16 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA1) RCV000031280 SCV000144216 uncertain significance Breast-ovarian cancer, familial 1 2004-02-20 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001358173 SCV001553844 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA1 c.81-11del variant was identified in the literature however the frequency of this variant in an affected population was not provided. The variant was also identified in ClinVar (6x, Benign by ENIGMA, Invitae, Color; Likely benign by Lab Corp and SCRP; Uncertain by BIC), or LOVD 3.0 (3x as benign). The variant was not identified in UMD-LSDB database. The variant was identified in control databases in 11 of 279514 chromosomes at a frequency of 0.00004 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2 of 24716 chromosomes (freq: 0.00008), Latino in 2 of 34920 chromosomes (freq: 0.00006), European (Non-Finnish) in 6 of 127620 chromosomes (freq: 0.00005), South Asian in 1 of 30012 chromosomes (freq: 0.00003); it was not observed in the Ashkenazi Jewish, East Asian, and Finish populations. Menendez et al. report an in vitro assay using RNA from lymphocyte cell cultures form a patient carrying this variant displaying that the variant had no effect on splicing (Menendez 2011). In addition Lindor et al. report a probability model that predicts this variant to be benign (Lindor 2012). The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

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