Submissions for variant NM_005343.4(HRAS):c.36C>T (p.Gly12=)

gnomAD frequency: 0.00004  dbSNP: rs727504424

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen RASopathy Variant Curation Expert Panel	RCV000522904	SCV000616474	likely benign	RASopathy	2017-04-18	reviewed by expert panel	curation	The filtering allele frequency of the c.36C>T (p.Gly12=) variant in the HRAS gene is 0.0461% (8/8626) of East Asian chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
Molecular Diagnostics Lab, Nemours Children's Health, Delaware	RCV000207496	SCV000263056	uncertain significance	Costello syndrome	2014-02-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000207496	SCV000560901	benign	Costello syndrome	2024-12-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586057	SCV000698557	benign	not provided	2016-07-11	criteria provided, single submitter	clinical testing	Variant summary: The HRAS c.36C>T (p.Gly12Gly) variant involves the alteration of a non-conserved nucleotide resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 8/120014 control chromosomes, observed exclusively in East Asian subpopulation at a frequency of 0.0009274 (8/8626). This frequency is about 371 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. The variant of interest has not, to our knowledge, been reported in affected individuals with NSRD via publications and/or reputable databases/clinical diagnostic laboratories. It has been classified as VUS by a lab without evidence to independently evaluate. Taken together, this variant is classified as Benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001813428	SCV002060962	likely pathogenic	Noonan syndrome and Noonan-related syndrome	2017-07-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003927887	SCV004742294	likely benign	HRAS-related disorder	2023-08-16	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).