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NM_001010942.3(RAP1B):c.451A>G (p.Lys151Glu) AND not provided

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 6, 2024
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:
RCV003456623.3

Allele description [Variation Report for NM_001010942.3(RAP1B):c.451A>G (p.Lys151Glu)]

NM_001010942.3(RAP1B):c.451A>G (p.Lys151Glu)

Gene:
RAP1B:RAP1B, member of RAS oncogene family [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
12q15
Genomic location:
Preferred name:
NM_001010942.3(RAP1B):c.451A>G (p.Lys151Glu)
Other names:
K151E
HGVS:
  • NC_000012.12:g.68656432A>G
  • NM_001010942.3:c.451A>GMANE SELECT
  • NM_001251917.2:c.325A>G
  • NM_001251918.2:c.325A>G
  • NM_001251921.2:c.394A>G
  • NM_001251922.2:c.310A>G
  • NM_015646.6:c.451A>G
  • NP_001010942.1:p.Lys151Glu
  • NP_001238846.1:p.Lys109Glu
  • NP_001238847.1:p.Lys109Glu
  • NP_001238850.1:p.Lys132Glu
  • NP_001238851.1:p.Lys104Glu
  • NP_056461.1:p.Lys151Glu
  • NC_000012.11:g.69050212A>G
Protein change:
K104E; LYS151GLU
Links:
OMIM: 179530.0001
Molecular consequence:
  • NM_001010942.3:c.451A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001251917.2:c.325A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001251918.2:c.325A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001251921.2:c.394A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001251922.2:c.310A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_015646.6:c.451A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004183562OMIM
no assertion criteria provided
Uncertain significance
(Mar 6, 2024) 		germlineliterature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

RAP1-mediated MEK/ERK pathway defects in Kabuki syndrome.

Bögershausen N, Tsai IC, Pohl E, Kiper PÖ, Beleggia F, Percin EF, Keupp K, Matchan A, Milz E, Alanay Y, Kayserili H, Liu Y, Banka S, Kranz A, Zenker M, Wieczorek D, Elcioglu N, Prontera P, Lyonnet S, Meitinger T, Stewart AF, Donnai D, et al.

J Clin Invest. 2015 Sep;125(9):3585-99. doi: 10.1172/JCI80102. Epub 2015 Aug 17.

PubMed [citation]
PMID:
26280580
PMCID:
PMC4588287

Details of each submission

From OMIM, SCV004183562.3

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

Description

This variant is classified as a variant of unknown significance because its contribution to a Kabuki-like syndrome (see 147920) has not been confirmed.

In a boy, born of unrelated Turkish parents, with features reminiscent of Kabuki syndrome, Bogershausen et al. (2015) identified a de novo heterozygous c.451A-G transition in the RAP1B gene, resulting in a lys151-to-glu (K151E) substitution at a conserved residue close to the GTP-binding site of RAP1B. The mutation, which was found by trio-based whole-exome sequencing and confirmed by Sanger sequencing, was not present in the Exome Variant Server or ExAC databases. Expression of the mutation in rap1b-null zebrafish failed to rescue convergent-extension (CE) defects, consistent with a loss of function. There was no evidence for a dominant-negative effect; thus the mutation likely resulted in haploinsufficiency. The patient had growth defects with short stature and microcephaly, developmental delay, seizures, congenital heart defects, and dysmorphic facial features, including long palpebral fissures, arched eyebrows, long eyelashes, dysplastic ears, and strabismus. He also had right tibial shortening and brachyphalangy. The patient had initially been diagnosed clinically with Hadziselimovic syndrome (612946).

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

Last Updated: Jun 9, 2024