Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000519017 | SCV000616469 | benign | RASopathy | 2017-04-18 | reviewed by expert panel | curation | The filtering allele frequency of the c.378A>G (p.Glu126=) variant in the HRAS gene is 0.095% (23/16510) of South Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BA1; PMID:29493581) |
Laboratory for Molecular Medicine, |
RCV000038462 | SCV000062139 | likely benign | not specified | 2010-01-27 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588072 | SCV000698558 | benign | not provided | 2016-10-03 | criteria provided, single submitter | clinical testing | Variant summary: The HRAS c.378A>G (p.Glu126Glu) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. 1/5 splice prediction tools predict that this variant may create a novel 3' splicing acceptor site. 2/5 splice prediction tools predict that this variant may weaken a cryptic 3' splicing acceptor site. ESE finder predicts that this variant may affect multiple ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 25/120908 control chromosomes at a frequency of 0.0002068, which is approximately 83 times the estimated maximal expected allele frequency of a pathogenic HRAS variant (0.0000025), suggesting this variant is likely a benign polymorphism. In addition, one clinical diagnostic laboratory classified this variant as likely benign. 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. Taken together, this variant is classified as benign. |
Labcorp Genetics |
RCV001081660 | SCV000758760 | benign | Costello syndrome | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000588072 | SCV001942936 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV001813237 | SCV002060516 | benign | Noonan syndrome and Noonan-related syndrome | 2020-09-21 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345262 | SCV002623301 | benign | Cardiovascular phenotype | 2021-05-18 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. |