ClinVar Miner

Submissions for variant NM_005343.4(HRAS):c.369C>T (p.Arg123=)

gnomAD frequency: 0.00006  dbSNP: rs200945755
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000520797 SCV000616470 benign RASopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.369C>T (p.Arg123=) variant in the HRAS gene is 0.089% (13/8638) of East 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)
PreventionGenetics, part of Exact Sciences RCV000242213 SCV000311012 likely benign not specified criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001079542 SCV000560899 benign Costello syndrome 2024-01-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000588992 SCV000698556 benign not provided 2017-01-23 criteria provided, single submitter clinical testing Variant summary: The HRAS c.369C>T (p.Arg123Arg) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. It is 81 nucleotides upstream from exon-intron boundary. 2/5 splice prediction tools predict a creation of cryptic splice donor site. ESE finder predicts that this variant may affect binding of ESE site(s). However, these predictions have yet to be confirmed by functional studies. This variant was found in 13/120964 control chromosomes, exclusively observed in the East Asian subpopulation at a frequency of 0.001505 (13/8638). This frequency is about 602 times the estimated maximal expected allele frequency of a pathogenic HRAS variant (0.0000025), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, one clinical diagnostic laboratory has 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. Taken together, this variant is classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV001813437 SCV002060515 benign Noonan syndrome and Noonan-related syndrome 2018-03-01 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV002257620 SCV002537978 likely benign Hereditary cancer-predisposing syndrome 2022-01-13 criteria provided, single submitter curation
Ambry Genetics RCV002347960 SCV002621871 likely benign Cardiovascular phenotype 2022-03-04 criteria provided, single submitter clinical testing This alteration is classified as likely 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.
CeGaT Center for Human Genetics Tuebingen RCV000588992 SCV004134984 likely benign not provided 2023-09-01 criteria provided, single submitter clinical testing HRAS: BP4, BP7
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000588992 SCV004564966 benign not provided 2023-09-20 criteria provided, single submitter clinical testing

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