NM_017774.3(CDKAL1):c.371+30101A>G AND Diabetes mellitus type 2

Clinical significance:Uncertain significance (Last evaluated: Sep 1, 2014)

Review status:(0/4) 0 stars out of maximum of 4 stars

no assertion criteria provided

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000001038.5

Allele description [Variation Report for NM_017774.3(CDKAL1):c.371+30101A>G]

NM_017774.3(CDKAL1):c.371+30101A>G

Gene:
CDKAL1:CDK5 regulatory subunit associated protein 1 like 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
6p22.3
Genomic location:
Preferred name:
NM_017774.3(CDKAL1):c.371+30101A>G
HGVS:
  • NC_000006.12:g.20679478A>G
  • NG_021195.1:g.150022A>G
  • NM_017774.3:c.371+30101A>G
  • NC_000006.11:g.20679709A>G
Links:
OMIM: 611259.0002; dbSNP: rs7756992
NCBI 1000 Genomes Browser:
rs7756992
Molecular consequence:
  • NM_017774.3:c.371+30101A>G - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Diabetes mellitus type 2 (NIDDM)
Synonyms:
DIABETES MELLITUS, TYPE 2, PROTECTION AGAINST; DIABETES MELLITUS, TYPE II, SUSCEPTIBILITY TO; NIDDM diabetes mellitus; See all synonyms [MedGen]
Identifiers:
MedGen: C0011860; OMIM: 125853; Human Phenotype Ontology: HP:0005978

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000021188OMIMno assertion criteria providedUncertain significance
(Sep 1, 2014)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

A variant in CDKAL1 influences insulin response and risk of type 2 diabetes.

Steinthorsdottir V, Thorleifsson G, Reynisdottir I, Benediktsson R, Jonsdottir T, Walters GB, Styrkarsdottir U, Gretarsdottir S, Emilsson V, Ghosh S, Baker A, Snorradottir S, Bjarnason H, Ng MC, Hansen T, Bagger Y, Wilensky RL, Reilly MP, Adeyemo A, Chen Y, Zhou J, Gudnason V, et al.

Nat Genet. 2007 Jun;39(6):770-5. Epub 2007 Apr 26.

PubMed [citation]
PMID:
17460697

Identification of a splicing variant that regulates type 2 diabetes risk factor CDKAL1 level by a coding-independent mechanism in human.

Zhou B, Wei FY, Kanai N, Fujimura A, Kaitsuka T, Tomizawa K.

Hum Mol Genet. 2014 Sep 1;23(17):4639-50. doi: 10.1093/hmg/ddu184. Epub 2014 Apr 23.

PubMed [citation]
PMID:
24760768

Details of each submission

From OMIM, SCV000021188.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

This variant, formerly titled DIABETES MELLITUS, NONINSULIN-DEPENDENT, SUSCEPTIBILITY TO, has been reclassified because this SNP has not been shown to be the causal variant accounting for association.

Steinthorsdottir et al. (2007) identified a variant in intron 5 of the CDKAL1 gene, rs7756992, that was associated with type 2 diabetes (125853) in individuals of European ancestry (allele-specific OR, 1.20; P = 7.7 x 10(-9)) and individuals from Hong Kong of Han Chinese ancestry (OR, 1.25; P = 0.00018). The ORs for homozygotes were 1.50 and 1.55 in the European and Hong Kong groups, respectively. The insulin response for homozygotes was approximately 20% lower than for heterozygotes or noncarriers (P = 2.5 x 10(-8)), suggesting that this variant confers risk of type 2 diabetes through reduced insulin secretion.

Zhou et al. (2014) found that expression of CDKAL1v1, but not full-length CDKAL1, was significantly reduced in individuals homozygous for the G allele of rs7756992. Human embryonic fibroblast cell lines homozygous for both the G allele of rs7756992 and the C allele of rs10946398 (611259.0001) also showed decreased expression of CDKAL1v1, but not CDKAL1. Zhou et al. (2014) hypothesized that the risk alleles of rs10946398 and rs7756992 influence alternative splicing of the CDKAL1 gene.

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

Last Updated: Mar 30, 2019

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