Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328211 | SCV001365420 | benign | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-10 | reviewed by expert panel | curation | The NM_004360.5(CDH1):c.1896C>T (p.His632=) variant has an allele frequency of 0.05030 (5%, 1255/24950 alleles, 32 homozygotes) in the African subpopulation of the gnomAD v2.1.1 cohort (BA1; BP2). Therefore, this variant meets criteria to be classified as benign. ACMG/AMP criteria applied, as specified by the CDH1 Variant Curation Expert Panel (Variant Interpretation Guidelines Version 3.1): BA1, BP2. |
Ambry Genetics | RCV000130151 | SCV000184986 | benign | Hereditary cancer-predisposing syndrome | 2014-11-18 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Prevention |
RCV000249039 | SCV000310123 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Laboratory Services, |
RCV000287503 | SCV000398572 | benign | Hereditary diffuse gastric adenocarcinoma | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
Color Diagnostics, |
RCV000130151 | SCV000537367 | benign | Hereditary cancer-predisposing syndrome | 2015-04-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000287503 | SCV000557383 | benign | Hereditary diffuse gastric adenocarcinoma | 2024-02-01 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001705928 | SCV000883548 | benign | not provided | 2023-11-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001705928 | SCV001912269 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000249039 | SCV002551785 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV000287503 | SCV003926866 | benign | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | BA1; BP2_Strong (PMID: 30311375) |
KCCC/NGS Laboratory, |
RCV003315887 | SCV004016998 | benign | Malignant tumor of prostate | 2023-07-07 | criteria provided, single submitter | clinical testing | |
True Health Diagnostics | RCV000130151 | SCV000787979 | likely benign | Hereditary cancer-predisposing syndrome | 2017-11-15 | no assertion criteria provided | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001355823 | SCV001550820 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The CDH1 p.His632= variant was identified in 7 of 716 proband chromosomes (frequency: 0.010) from Polish, Italian and multiethnic cohorts of individuals or families with hereditary diffuse gastric cancer, nonhereditary or at risk gastric cancer and breast cancer (invasive lobular carcinoma), and was present in 7 of 304 control chromosomes (frequency: 0.02) from healthy individuals (Jakubowska 2010, Oliveira 2002, Valente 2014 , Garziera 2013). In one study, individuals found to carry the variant were those at risk of gastric cancer but not with sporadic gastric cancer (Garziera 2013). The variant has been reported as a polymorphism (frequency unspecified), in several studies (Berx 1997, Gayther 1998). The variant was identified in dbSNP (ID: rs33969373) “With Benign allele”, ClinVar database (classification benign by Ambry Genetics, Prevention Genetics, Illumina, Color Genomics and Invitae), Clinvitae (3X classified as benign), Cosmic (2X in a haemangioblastoma and thyroid tumor), and the Zhejiang Colon Cancer Database (3X); and was not identified in MutDB, or Insight Colon Cancer Gene Variant Database. The variant was also identified in control databases in 3105 (57 homozygous) of 277164 chromosomes at a frequency of 0.0112, increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Consortium Feb 27 2017); being identified in the following populations at a frequency greater than 1%: African in 1191 of 24012 chromosome (freq: 0.05), Other in 128 of 6464 chromosomes (freq. 0.02), Latino in 477 of 34418 chromosomes (freq. 0.014), and in Ashkenazi Jewish in 103 of 10152 chromosomes (freq. 0.010). The p.His632His variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. | |
Genome Diagnostics Laboratory, |
RCV000249039 | SCV001809251 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000249039 | SCV001906012 | benign | not specified | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000249039 | SCV001923994 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000249039 | SCV001959791 | benign | not specified | no assertion criteria provided | clinical testing |