ClinVar Miner

Submissions for variant NM_002524.5(NRAS):c.35G>A (p.Gly12Asp) (rs121913237)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Database of Curated Mutations (DoCM) RCV000436228 SCV000503718 likely pathogenic Acute myeloid leukemia 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417702 SCV000503719 likely pathogenic Multiple myeloma 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000427949 SCV000503720 pathogenic Neoplasm of the large intestine 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000439064 SCV000503721 pathogenic Non-small cell lung cancer 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000417869 SCV000503722 pathogenic Cutaneous melanoma 2014-10-02 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000430706 SCV000503723 likely pathogenic Malignant neoplasm of body of uterus 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000440963 SCV000503724 likely pathogenic Malignant melanoma of skin 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000424239 SCV000503725 likely pathogenic Myelodysplastic syndrome 2016-05-31 no assertion criteria provided literature only
Database of Curated Mutations (DoCM) RCV000434517 SCV000503726 likely pathogenic Adenocarcinoma of stomach 2016-05-31 no assertion criteria provided literature only
GeneDx RCV000158980 SCV000208919 pathogenic not provided 2016-01-06 criteria provided, single submitter clinical testing The G12D missense change in the NRAS gene has not been reported as a disease-causing variant or as a benign polymorphism to our knowledge. The G12D amino acid substitution is non-conservative with a neutral and non-polar residue (Gly) being replaced by a negatively charged and polar residue (Asp). The residue at which this substitution occurs is highly conserved in the protein. Other missense variants at this residue (G12V, G12S, G12R) have been reported previously as somatic variants in association with several different types of cancer (Catalogue of Somatic Mutations in Cancer; Cirstea et al., 2010), primarily in haematopoietic and lymphoid tissues. Another missense variants at a neighboring codon (G13D) has been reported as a germline mutation (Filippi et al., 2009; Oliviera et al., 2007). In Filippi et al., the patient with the G13D variant was described as having dysmorphic features (including macrocephaly, bilateral epicanthal folds and cafe-au-lait spots) in addition to clinical and hematological features consistent with a diagnosis of juvenile myelomonocytic leukemia (JMML) (Filippi et al., 2009). The presence of the G12D variant is consistent with a diagnosis of an NRAS-related disorder and the reported diagnosis of JMML.
OMIM RCV000032849 SCV000056618 pathogenic Epidermal nevus 2013-12-05 no assertion criteria provided literature only
OMIM RCV000144963 SCV000191990 pathogenic Juvenile myelomonocytic leukemia 2013-12-05 no assertion criteria provided literature only

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