ClinVar Miner

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

dbSNP: rs121913250
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Total submissions: 16
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158985 SCV000208924 pathogenic not provided 2015-06-02 criteria provided, single submitter clinical testing This mutation is denoted as c.34 G>C at the cDNA level or p.Gly12Arg (G12R) at the protein level. The G12R missense mutation in the NRAS gene has not been published as a germline mutation or benign polymorphism, to our knowledge. G12R has been reported previously as a somatic mutation in association with several different types of cancer (Catalogue of Somatic Mutations in Cancer; Cirstea et al., 2010), primarily in haematopoietic and lymphoid tissues. A different missense substitution at the same position (G12C) has been seen at GeneDx several times and another (G12V) also has been reported previously as a somatic mutation (Catalogue of Somatic Mutations in Cancer; Cirstea et al., 2010). In Filippi et al., a patient with the adjacent G13D mutation was described as having dysmorphic features (including macrocephaly, bilateral epicanthal folds and cafe-au-lait spots) in addition to clinical and heamological features consistent with a diagnosis of juvenile myelomonocytic leukemia (JMML) (Filippi et al., 2009). The variant is found in NOONAN panel(s).
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV001526619 SCV001737049 pathogenic Increased nuchal translucency criteria provided, single submitter clinical testing
3billion 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
Database of Curated Mutations (DoCM) RCV000444217 SCV000503736 pathogenic Melanoma 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000425150 SCV000503737 pathogenic Non-small cell lung carcinoma 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000435447 SCV000503738 likely pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420396 SCV000503739 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430635 SCV000503740 likely pathogenic Chronic myelogenous leukemia, BCR-ABL1 positive 2015-07-14 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000438291 SCV000503741 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000420637 SCV000503742 likely pathogenic Gastric adenocarcinoma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430032 SCV000503743 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440262 SCV000503744 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000423088 SCV000503745 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only

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