Submissions for variant NM_005343.4(HRAS):c.357C>T (p.Asp119=)

gnomAD frequency: 0.00121  dbSNP: rs111352454

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000522686	SCV000616471	benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.357C>T (p.Asp119=) variant in the HRAS gene is 0.129% (102/66416) of European 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, Mass General Brigham Personalized Medicine	RCV000038458	SCV000062134	benign	not specified	2011-08-18	criteria provided, single submitter	clinical testing	Asp119Asp in exon 4 of HRAS: This variant is not expected to have clinical signi ficance because it has been identified in 8/214(3.7%) chromosomes (rs111352454). In addition, this variant does not alter an amino acid residue and is not loca ted near a splice junction. Furthermore, this variant has previously been identi fied in our laboratory in an individual with a de novo variant in BRAF and in an unaffected parent of that individual.
Invitae	RCV000227939	SCV000288857	benign	Costello syndrome	2024-01-29	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000038458	SCV000703503	benign	not specified	2016-12-16	criteria provided, single submitter	clinical testing
GeneDx	RCV001711139	SCV001942933	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813236	SCV002060513	benign	Noonan syndrome and Noonan-related syndrome	2020-07-01	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV002257371	SCV002537976	benign	Hereditary cancer-predisposing syndrome	2020-02-24	criteria provided, single submitter	curation
Ambry Genetics	RCV002453280	SCV002614122	likely benign	Cardiovascular phenotype	2019-11-19	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.
Fulgent Genetics, Fulgent Genetics	RCV002477043	SCV002798843	likely benign	Large congenital melanocytic nevus; Linear nevus sebaceous syndrome; Malignant tumor of urinary bladder; Costello syndrome; Epidermal nevus; Thyroid cancer, nonmedullary, 2	2021-07-26	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001711139	SCV004134985	benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	HRAS: BP4, BP7, BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003924885	SCV004745783	benign	HRAS-related disorder	2019-10-01	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000038458	SCV001924427	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001711139	SCV001956314	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001711139	SCV001963803	likely benign	not provided		no assertion criteria provided	clinical testing