NM_004985.5(KRAS):c.35G>A (p.Gly12Asp) AND Autoimmune lymphoproliferative syndrome type 4

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 10, 2012
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000144970.14

Allele description [Variation Report for NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)]

NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)

Gene:
KRAS:KRAS proto-oncogene, GTPase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12p12.1
Genomic location:
Preferred name:
NM_004985.5(KRAS):c.35G>A (p.Gly12Asp)
HGVS:
  • NC_000012.12:g.25245350C>T
  • NG_007524.2:g.10654G>A
  • NM_001369786.1:c.35G>A
  • NM_001369787.1:c.35G>A
  • NM_004985.5:c.35G>AMANE SELECT
  • NM_033360.4:c.35G>A
  • NP_001356715.1:p.Gly12Asp
  • NP_001356716.1:p.Gly12Asp
  • NP_004976.2:p.Gly12Asp
  • NP_203524.1:p.Gly12Asp
  • LRG_344t1:c.35G>A
  • LRG_344t2:c.35G>A
  • LRG_344:g.10654G>A
  • LRG_344p1:p.Gly12Asp
  • LRG_344p2:p.Gly12Asp
  • NC_000012.11:g.25398284C>T
  • NG_007524.1:g.10571G>A
  • NM_004985.3:c.35G>A
  • NM_004985.4:c.35G>A
  • NM_033360.2:c.35G>A
  • NM_033360.3:c.35G>A
  • P01116:p.Gly12Asp
Protein change:
G12D; GLY12ASP
Links:
UniProtKB: P01116#VAR_016026; OMIM: 190070.0005; OMIM: 190070.0025; dbSNP: rs121913529
NCBI 1000 Genomes Browser:
rs121913529
Molecular consequence:
  • NM_001369786.1:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369787.1:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004985.5:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_033360.4:c.35G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
effect on catalytic protein function [Variation Ontology: 0008]

Condition(s)

Name:
Autoimmune lymphoproliferative syndrome type 4
Synonyms:
AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME, TYPE IV; RAS-associated autoimmune leukoproliferative disorder
Identifiers:
MONDO: MONDO:0013767; MedGen: C2674723; Orphanet: 268114; OMIM: 614470

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000191997OMIM
no assertion criteria provided
Pathogenic
(Jun 10, 2012)
somaticliterature only

PubMed (8)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedsomaticnot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Detection of point mutations in the Kirsten-ras oncogene provides evidence for the multicentricity of pancreatic carcinoma.

Motojima K, Urano T, Nagata Y, Shiku H, Tsurifune T, Kanematsu T.

Ann Surg. 1993 Feb;217(2):138-43.

PubMed [citation]
PMID:
8439212
PMCID:
PMC1242752

Clinicopathologic significance of the K-ras gene codon 12 point mutation in stomach cancer. An analysis of 140 cases.

Lee KH, Lee JS, Suh C, Kim SW, Kim SB, Lee JH, Lee MS, Park MY, Sun HS, Kim SH.

Cancer. 1995 Jun 15;75(12):2794-801.

PubMed [citation]
PMID:
7773929
See all PubMed Citations (8)

Details of each submission

From OMIM, SCV000191997.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (8)

Description

Pancreatic Carcinoma, Somatic

Motojima et al. (1993) identified mutations in KRAS codon 12 in 46 of 53 pancreatic carcinomas (260350). In 2 of these 46 tumors, the mutations were gly12-to-asp (G12D) and gly12-to-val (G12V; 190070.0006), respectively.

Gastric Cancer, Somatic

Lee et al. (1995) found mutations in codon 12 of the KRAS gene in 9 of 140 cases of gastric cancer (613659); 2 cases had G12D.

Epidermal Nevus, Somatic

Bourdeaut et al. (2010) found somatic mosaicism for the G12D mutation in a female infant with an epidermal nevus (162900) who developed a uterovaginal rhabdomyosarcoma at age 6 months. There was also an incidental finding of micropolycystic kidneys without impaired renal function. Both the epidermal nevus and the rhabdomyosarcoma carried the G12D mutation, which was not found in normal dermal tissue, bone, cheek swap, or lymphocytes. No renal tissue was available for study. The phenotype was consistent with broad activation of the KRAS pathway.

Hafner et al. (2012) identified a somatic G12D mutation in 1 of 72 keratinocytic epidermal nevi.

Nevus Sebaceous, Somatic

Groesser et al. (2012) identified a somatic G12D mutation in 2 of 65 (3%) nevus sebaceous tumors (see 162900). One of the tumors also carried a somatic mutation in the HRAS gene (G13R; 190020.0017).

Schimmelpenning-Feuerstein-Mims Syndrome, Somatic Mosaic

The KRAS G12D mutation was also found in somatic mosaic state in a patient with Schimmelpenning-Feuerstein-Mims syndrome (163200) who was originally reported by Rijntjes-Jacobs et al. (2010). Groesser et al. (2012) postulated that the mosaic mutation likely extends to extracutaneous tissues in that disorder, which could explain the phenotypic pleiotropy.

Juvenile Myelomonocytic Leukemia, Somatic

In white blood cells derived from a 22-month-old girl with juvenile myelomonocytic leukemia (JMML; 607785), Matsuda et al. (2007) identified a somatic heterozygous G12D mutation in the KRAS gene.

RAS-associated Autoimmune Leukoproliferative Disorder, Somatic

In hematologic cells derived from a girl with RAS-associated autoimmune leukoproliferative disorder (RALD; 614470), Niemela et al. (2010) identified a somatic heterozygous G12D mutation in the KRAS gene.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1somaticnot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 24, 2024