Due to a production error, there was a mistake in Table 2 as published. Some BRCA1 variants were incorrectly listed. The correct Table 2 appears below. The publisher apologizes for this mistake.
Table 2
| BRCA1 VUS | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Nucleotide change HGVS nomenclature | Amino acid change | Type of VUS | ClinVar classification | ENIGMA/VarSome | PolyPhen-2/SIFT | HCI Prior/Align-GVGDa | BC patients | OC patients | ExAC/GnomADb | pCR |
| c.3367G>T | p.Asp1123Tyr | MISSENSE | CIP | NYR/VUS | Light/ Damaging | 0.02/C0 | 2 | \ | 0.00002/ 0.00001 | OCCR |
| c.889A>C | p.Met297Leu | MISSENSE | CIP | NYR/VUS | Light/ Tolerated | 0.02/C0 | 1 | \ | \ | \ |
| c.2417C>G | p.Ala806Gly | \ | NF | No data | Light/- | 0.02/C0 | 1 | \ | \ | OCCR |
| c.81-12dupC | \ | IVS | NF | No data | \ | \ | 1 | \ | \ | \ |
| c.301+6T>C | \ | IVS | VUS | NYR/VUS | \ | 0.34/\ | 1 | \ | 0.00002/ 0.00001 | BCCR1 |
| c.4063_4065delAAT | p.Asn1355del | In-frame DEL | CIP | NYR/VUS | \ | \ | 1 | \ | \ | \ |
| c.4460A>G | p.Lys1487Arg | MISSENSE | VUS | NYR/VUS | Light/ Tolerated-Damaging | 0.02/C0 | 1 | \ | \ | BCCR2 |
| c.1881C>G | p.Val627= | synonymous | CIP | NYR/LBV | \ | 0.02/\ | 1 | 1 | -/0.00003 | OCCR |
| c.2447A>G* | p.His816Arg | MISSENSE | CIP | NYR/VUS | Light/ Tolerated | 0.02/C0 | 1 | \ | 0.00001/ 0.00002 | OCCR |
| c.3952A>G | p.Ile1318Val | MISSENSE | VUS | NYR/VUS | Light/ Tolerated | 0.02/C0 | 1 | \ | \ | OCCR |
| c.742A>C | p.Thr248Pro | MISSENSE | CIP | NYR/VUS | Light/ Tolerated | 0.02/C0 | 1 | \ | \ | \ |
| c.4185+8_4185+8delG | \ | IVS | NF | NF/VUS | \ | \ | 1 | \ | \ | \ |
| c.4054G>A | p.Glu1352Lys | MISSENSE | VUS | NYR/VUS | Light/ Damaging | 0.02/C0 | 1 | \ | 0.00004/ 0.00002 | OCCR |
| c.4739C>T | p.Ser1580Phe | MISSENSE | VUS | NYR/VUS | Light/ Damaging | 0.02/C15 | 1 | \ | \ | BCCR2 |
| c.4009G>C | p.Asp1337His | MISSENSE | VUS | NYR/VUS | Light/ Tolerated | 0.02/C0 | 1 | \ | \ | OCCR |
| c.2218G>C | p.Val740Leu | MISSENSE | VUS | NYR/VUS | Light/ Tolerated | 0.02/C0 | 1 | \ | \ | OCCR |
| c.4096+3A>G | \ | IVS | VUS | VUS/LPV | \ | 0.97/\ | 1 | 1 | \ | \ |
| c.4963T>G | p.Ser1655Ala | MISSENSE | Not provided | NYR/LPV | Light/ Damaging | 0.03/C0 | \ | 3 | \ | \ |
| c.4543G>A | p.Gly1515Arg | \ | NF | NF/VUS | Light/ Tolerated | 0.02/C0 | \ | 1 | \ | BCCR2 |
| c.1007C>T | p.Thr336Ile | \ | NF | NF/VUS | Light/ Damaging | 0.02/C0 | \ | 1 | \ | \ |
| c.1705A>G | p.Asn569Asp | MISSENSE | VUS | NYR/VUS | Light/ Tolerated | 0.02/C0 | \ | 1 | \ | OCCR |
BRCA1 gene variants of unclear significance harbored by patients with breast and ovarian cancers.
*This BRCA1 variant is simultaneously present together with the BRCA2 VUS c.8262T>G (reported in Table 3) in one of probands with BC. Novel variants are reported in bold.
The Align-GVGD program predicts where the variants in BRCA1 and BRCA2 genes fall in a spectrum ranging from enriched deleterious to enriched neutral. The prediction classes form a spectrum (C0, C15, C25, C35, C45, C55, C65) with C65 most likely to interfere with protein function and C0 least likely. The HCI Prior database, based on Align-GVGD scores, defines four classes of probability of pathogenicity: C0 = 0.03; C15-C25 = 0.29; C35-C55 = 0.66; C65 = 0.81.
The Exome Aggregation Consortium (ExAC) and Genome Aggregation Database (gnomAD) aggregate both exome and genome sequencing data from a wide variety of large-scale sequencing projects, by providing values of allelic frequency.
BC, breast cancer; BCCR, breast cancer cluster region; CIP, conflicting interpretations of pathogenicity; DEL, deletion; HGVS, Human Genome Variant Society; IVS, intronic variants; LBV, likely benign variant; LPV, likely pathogenic variant; NF, not found; NYR, not yet reviewed; OC, ovarian cancer; OCCR, ovarian cancer cluster region; pCR, putative cluster region (defined by Rebbeck et al.); VUS, variant of uncertain significance.
The original version of this article has been updated.
Summary
Keywords
BRCA1, BRCA2, breast cancer, genetic testing, ovarian cancer, variants of uncertain significance (VUS)
Citation
Frontiers Production Office (2022) Erratum: Prevalence and Spectrum of Germline BRCA1 and BRCA2 Variants of Uncertain Significance in Breast/Ovarian Cancer: Mysterious Signals From the Genome. Front. Oncol. 12:920342. doi: 10.3389/fonc.2022.920342
Received
14 April 2022
Accepted
14 April 2022
Published
04 May 2022
Approved by
Frontiers Editorial Office, Frontiers Media SA, Switzerland
Volume
12 - 2022
Updates
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This article was submitted to Cancer Genetics, a section of the journal Frontiers in Oncology
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