ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2439+10C>T

gnomAD frequency: 0.00057  dbSNP: rs35236080
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Total submissions: 20
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000123248 SCV000166554 benign Hereditary diffuse gastric adenocarcinoma 2021-12-17 criteria provided, single submitter clinical testing
GeneDx RCV000212388 SCV000167599 benign not specified 2013-12-27 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.
Ambry Genetics RCV000128981 SCV000172867 likely benign Hereditary cancer-predisposing syndrome 2015-02-12 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl RCV000123248 SCV000488637 likely benign Hereditary diffuse gastric adenocarcinoma 2016-05-10 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000128981 SCV000684434 likely benign Hereditary cancer-predisposing syndrome 2015-04-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588639 SCV000698384 benign not provided 2016-07-25 criteria provided, single submitter clinical testing Variant summary: The CDH1 c.2439+10C>T variant involves the alteration of a non-conserved intronic nucleotide. One in silico tool (MutationTaster) predicts a benign outcome for this variant. 3/5 splice prediction tools predict a significant impact on normal splicing. However, these predictions are not definitive and have not been confirmed by functional studies. This variant was found in 67/120124 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0009851 (65/65982). This frequency is about 35 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 European (Non-Finnish) origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as Benign.
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000128981 SCV000803169 likely benign Hereditary cancer-predisposing syndrome 2018-05-23 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000212388 SCV000806660 benign not specified 2017-12-12 criteria provided, single submitter clinical testing
Mendelics RCV000123248 SCV000839098 likely benign Hereditary diffuse gastric adenocarcinoma 2018-07-02 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588639 SCV000889251 benign not provided 2019-03-07 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000588639 SCV001157630 benign not provided 2021-05-10 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001262766 SCV001440751 likely benign Familial cancer of breast 2019-01-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001798406 SCV002043272 likely benign Breast and/or ovarian cancer 2021-05-05 criteria provided, single submitter clinical testing
Genetic Services Laboratory,University of Chicago RCV000212388 SCV002064749 likely benign not specified 2020-09-02 criteria provided, single submitter clinical testing
Sema4,Sema4 RCV000128981 SCV002529138 benign Hereditary cancer-predisposing syndrome 2020-11-12 criteria provided, single submitter curation
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001356066 SCV001551126 likely benign Malignant tumor of breast no assertion criteria provided clinical testing The CDH1 c.2439+10C>T variant was identified in 1 of 162 proband chromosomes (frequency: 0.006) from individuals or families with non-syndromic orofacial clefts and an unknown family history of hereditary diffuse gastric cancer (Vogelaar 2013). The variant was also identified in dbSNP (ID: rs35236080) as "With other allele" and ClinVar (classified as benign by Invitae, GeneDx and one other clinical laboratory; as likely benign by Ambry Genetics, Counsyl, Color Genomics, and two other clinical laboratories). The variant was not identified in the Zhejiang University Database. The variant was identified in control databases in 142 of 276210 chromosomes (1 homozygous) at a frequency of 0.0005, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European in 129 of 126428 chromosomes (freq: 0.001), African in 1 of 23894 chromosomes (freq: 0.00004), Other in 2 of 6448 chromosomes (freq: 0.0003), and Latino in 10 of 34374 chromosomes (freq: 0.0003), while the variant was not observed in the Ashkenazi Jewish, East Asian, Finnish, or South Asian populations. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information, the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV000588639 SCV001741016 likely benign not provided no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000588639 SCV001809482 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000588639 SCV001919287 likely benign not provided no assertion criteria provided clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000212388 SCV002551797 likely benign not specified 2022-01-07 no assertion criteria provided clinical testing

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