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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