ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8486A>G (p.Gln2829Arg) (rs80359100)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031744 SCV000327902 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000510027 SCV000607759 uncertain significance Hereditary cancer-predisposing syndrome 2019-09-04 criteria provided, single submitter clinical testing Insufficient or conflicting evidence;Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000590582 SCV000695156 likely pathogenic Hereditary breast and ovarian cancer syndrome 2017-02-07 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.8486A>G (p.Gln2829Arg) variant involves the alteration of a conserved nucleotide, which 4/5 in silico tools predict a damaging outcome for this variant. This variant is located at < 2nt from the intron-exon junction, which 3/5 splice prediction tools predict a significant impact on normal splicing and ESE finder predicting that this variant may affect ESE binding sites for SRp50 and SF2/ASF and might add binding sites for SRp55. One functional study, Houdayer _2012, testing this variant in lymphocytes found it to cause an inframe mutation resulting in exon 19 skipping, with no wildtype transcript being produced. This variant is absent in 120974 control chromosomes, which does not exceed the estimated maximum expected allele frequency for a pathogenic BRCA2 variant of 1/1333. The variant was observed in affected individuals via publications. Multiple clinical diagnostic laboratories/reputable databases have reported the variant with conflicting classifications, predominantly as "likely pathogenic/pathogenic," and others classifying it as "uncertain significance." Taken together, this variant is classified as likely pathogenic.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001170976 SCV001333636 likely pathogenic Breast and/or ovarian cancer 2017-11-20 criteria provided, single submitter clinical testing
Sharing Clinical Reports Project (SCRP) RCV000031744 SCV000054351 uncertain significance Breast-ovarian cancer, familial 2 2012-05-01 no assertion criteria provided clinical testing
Division of Human Genetics,Medical University Innsbruck RCV000031744 SCV000212031 likely pathogenic Breast-ovarian cancer, familial 2 2015-02-11 no assertion criteria provided clinical testing

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