Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328337 | SCV001943362 | likely benign | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-17 | reviewed by expert panel | curation | c.387+6T>C is an intronic variant in the splice donor region of intron 3. This variant has an allele frequency of 0.0001 (5/34548 alleles) in the gnomAD v2.1 Latino/admixed American sub-population (http://gnomad.broadinstitute.org). This variant has been reported in at least 13 individuals without DGC, SRC tumours or LBC and whose families do not suggest HDGC (BS2; SCV000637825.4). This variant is predicted to have no impact on splicing by multiple in silico splice site predictors (BP4; SpliceAI, varSEAK, MaxEntScan). In summary, this variant meets criteria to be classified as likely benign based on ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BS2, BP4. |
Gene |
RCV000589852 | SCV000529222 | likely benign | not provided | 2018-06-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000539158 | SCV000637825 | likely benign | Hereditary diffuse gastric adenocarcinoma | 2023-09-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589852 | SCV000698399 | uncertain significance | not provided | 2016-09-26 | criteria provided, single submitter | clinical testing | Variant summary: The CDH1 c.387+6T>C variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESEfinder predicts a gain of binding motif for splicing enhancer SC15. However, these predictions have yet to be confirmed by functional studies. This variant was found in 1/119366 control chromosomes, predominantly observed in the Latino subpopulation at a frequency of 0.000088 (1/11358). This frequency is about 3 times the estimated maximal expected allele frequency of a pathogenic CDH1 variant (0.0000283), suggesting this is likely a benign polymorphism found primarily in the populations of Latino origin. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Because of the absence of clinical information and the lack of functional studies, the variant is classified as a variant of uncertain significance (VUS)-possibly benign until additional information becomes available. |
Color Diagnostics, |
RCV000776451 | SCV000911983 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-04-09 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000589852 | SCV004220831 | likely benign | not provided | 2023-03-10 | criteria provided, single submitter | clinical testing |