ClinVar Miner

Submissions for variant NM_001164617.2(GPC3):c.1236-8T>C (rs182950534)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001083432 SCV000288563 benign Wilms tumor 1 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000422666 SCV000519051 benign not specified 2016-10-20 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Athena Diagnostics Inc RCV000711833 SCV000842238 benign not provided 2017-09-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000422666 SCV000859933 likely benign not specified 2018-03-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000422666 SCV000917488 benign not specified 2018-09-14 criteria provided, single submitter clinical testing Variant summary: GPC3 c.1167-8T>C alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0025 in 199497 control chromosomes in the gnomAD database, including 1 homozygote and 179 hemizygotes. The observed variant frequency is approximately 39459-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in GPC3 causing Wilms Tumor, Type 1 phenotype (6.3e-08), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1167-8T>C in individuals affected with Wilms Tumor, Type 1 and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

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