Submissions for variant NM_002524.5(NRAS):c.34G>C (p.Gly12Arg)

dbSNP: rs121913250

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158985	SCV000208924	pathogenic	not provided	2024-01-02	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are a common cause of disease and they are underrepresented in the general population; This variant is associated with the following publications: (PMID: 31697451, 28594414)
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001526619	SCV001737049	pathogenic	Increased nuchal translucency		criteria provided, single submitter	clinical testing
3billion, Medical Genetics	RCV001781335	SCV002318830	pathogenic	Noonan syndrome 6	2022-03-22	criteria provided, single submitter	clinical testing	Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000040469). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least one similarly affected unrelated individual (PMID:28594414). Different missense change at the same codon have been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000039648,VCV000040468,VCV000040470,VCV000177778, PMID:30417923,28594414,32888943,28594414,23334668). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.713>=0.6, 3CNET: 0.998>=0.75). A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein	RCV001781335	SCV002512401	pathogenic	Noonan syndrome 6	2021-11-27	criteria provided, single submitter	clinical testing	ACMG classification criteria: PS4 supporting, PM1 moderate, PM2 moderate, PM6 strong, PP3 supporting
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV001781335	SCV003843224	pathogenic	Noonan syndrome 6	2021-02-08	criteria provided, single submitter	clinical testing
Genesolutions, Medical Genetics Institutes, Ho Chi Minh City, Vietnam	RCV001781335	SCV003934964	pathogenic	Noonan syndrome 6	2022-06-22	criteria provided, single submitter	clinical testing