NM_001130823.3(DNMT1):c.3668G>A (p.Arg1223His) AND Beckwith-Wiedemann syndrome

Clinical significance:Uncertain significance

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:
RCV000625706.1

Allele description [Variation Report for NM_001130823.3(DNMT1):c.3668G>A (p.Arg1223His)]

NM_001130823.3(DNMT1):c.3668G>A (p.Arg1223His)

Gene:
DNMT1:DNA methyltransferase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.2
Genomic location:
Preferred name:
NM_001130823.3(DNMT1):c.3668G>A (p.Arg1223His)
HGVS:
  • NC_000019.10:g.10140184C>T
  • NG_028016.3:g.96103G>A
  • NM_001130823.3:c.3668G>AMANE SELECT
  • NM_001318730.2:c.3620G>A
  • NM_001318731.2:c.3305G>A
  • NM_001379.4:c.3620G>A
  • NP_001124295.1:p.Arg1223His
  • NP_001305659.1:p.Arg1207His
  • NP_001305660.1:p.Arg1102His
  • NP_001370.1:p.Arg1207His
  • LRG_362t1:c.3668G>A
  • LRG_362:g.96103G>A
  • NC_000019.9:g.10250860C>T
  • NM_001130823.1:c.3668G>A
Protein change:
R1102H
Links:
dbSNP: rs757460628
NCBI 1000 Genomes Browser:
rs757460628
Molecular consequence:
  • NM_001130823.3:c.3668G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318730.2:c.3620G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001318731.2:c.3305G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001379.4:c.3620G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
variation affecting protein function [Variation Ontology: 0003]

Condition(s)

Name:
Beckwith-Wiedemann syndrome (BWS)
Synonyms:
Exomphalos macroglossia gigantism syndrome; EMG Syndrome
Identifiers:
MONDO: MONDO:0007534; MedGen: C0004903; Orphanet: 116; OMIM: 130650

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000599436Genetics and Molecular Pathology Laboratory,Hudson Institute of Medical Researchno assertion criteria providedUncertain significancegermline, not applicableresearch

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyes1not providednot providednot providednot providedresearch
not providednot applicablenot applicablenot providednot providednot providednot providednot providedresearch

Details of each submission

From Genetics and Molecular Pathology Laboratory,Hudson Institute of Medical Research, SCV000599436.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
11not providednot providedresearchnot provided
2not providednot providednot providednot providedresearchnot provided

Description

Screening DNMT1 by high resolution melting and confirmation with Sanger sequencing was used to identify the variant rs757460628 encoding DNMT1: NP_001124295 p.Arg1223His in a population of Beckwith Wiedemann syndrome cases with loss of methylation at 11p15.5 Imprinting centre 2. GFP-DNMT1 fusion protein encoding the variant was compared to wild-type GFP-DNMT1 fusion protein in a functional assay measuring the interaction between enzyme and DNA in a trapping assay described in Frauer and Leonhardt (2009), (A versatile non-radioactive assay for DNA methyltransferase activity and DNA binding. Nucleic Acids Res, 37, e22). The variant DNMT1: NP_001124295 p.Arg1223His was shown to have an approximately 70% reduction of trapping activity in this assay when compared to wild-type GFP-DNMT1 protein.

Description

This variant was identified in heterozygous form in 1 of 53 cases with Beckwith Wiedemann syndrome with loss of KCNQ1OT1 at Imprinting centre 2 on 11p15.5. The variant frequency in dbSNP is 0.00002.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided
2not applicablenot applicablenot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 27, 2021

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