Resolving pathogenicity classification for the CDH1 c.[715G>A] (p.Gly239Arg) variant Journal Article
| Authors: | Yelskaya, Z.; Arnold, A. G.; Marcell, V. J.; Tang, L. H.; Salo-Mullen, E. E.; Strong, V. E.; Stadler, Z. K.; Zhang, L. |
| Article Title: | Resolving pathogenicity classification for the CDH1 c.[715G>A] (p.Gly239Arg) variant |
| Abstract: | Hereditary Diffuse Gastric Cancer (HDGC) syndrome is associated with CDH1 germline likely pathogenic/pathogenic variants. Carriers of CDH1 germline likely pathogenic/pathogenic variants are predisposed to diffuse gastric cancer and lobular breast cancer. This study aims to classify the CDH1 c.[715G>A] missense variant identified in a diffuse gastric cancer prone family by performing splicing studies. RT-PCR and subsequent cloning experiments were performed to investigate whether this variant completely disrupts normal splicing. This variant preferentially abolishes normal splicing through activation of a cryptic 3′ acceptor splice site within exon 6 of CDH1, presumably leading to a premature protein truncation within first extracellular domain repeat of E-cadherin protein. Our results contributed to evidence necessary to resolve pathogenicity classification of this variant, indicating that this variant is to be classified as pathogenic. © 2021, The Author(s), under exclusive licence to European Society of Human Genetics. |
| Journal Title: | European Journal of Human Genetics |
| Volume: | 29 |
| Issue: | 7 |
| ISSN: | 1018-4813 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2021-07-01 |
| Start Page: | 1103 |
| End Page: | 1109 |
| Language: | English |
| DOI: | 10.1038/s41431-021-00825-w |
| PUBMED: | 33619332 |
| PROVIDER: | scopus |
| PMCID: | PMC8298625 |
| DOI/URL: | |
| Notes: | Article -- Correction issued, see DOI 10.1038/s41431-021-00825-w -- Export Date: 1 September 2021 -- Source: Scopus |
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