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NM_006892.4(DNMT3B):c.2292G>T (p.Arg764Ser) AND Immunodeficiency-centromeric instability-facial anomalies syndrome 1

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 28, 2017
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000544568.6

Allele description [Variation Report for NM_006892.4(DNMT3B):c.2292G>T (p.Arg764Ser)]

NM_006892.4(DNMT3B):c.2292G>T (p.Arg764Ser)

Gene:
DNMT3B:DNA methyltransferase 3 beta [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
20q11.21
Genomic location:
Preferred name:
NM_006892.4(DNMT3B):c.2292G>T (p.Arg764Ser)
HGVS:
  • NC_000020.11:g.32805398G>T
  • NG_007290.1:g.48014G>T
  • NM_001207055.2:c.2046-2364G>T
  • NM_001207056.2:c.1944-2364G>T
  • NM_006892.4:c.2292G>TMANE SELECT
  • NM_175848.2:c.2232G>T
  • NM_175849.2:c.2172-2364G>T
  • NM_175850.3:c.2268G>T
  • NP_008823.1:p.Arg764Ser
  • NP_787044.1:p.Arg744Ser
  • NP_787046.1:p.Arg756Ser
  • LRG_56t1:c.2292G>T
  • LRG_56:g.48014G>T
  • NC_000020.10:g.31393204G>T
  • NM_006892.3:c.2292G>T
Protein change:
R744S
Links:
dbSNP: rs759448571
NCBI 1000 Genomes Browser:
rs759448571
Molecular consequence:
  • NM_001207055.2:c.2046-2364G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001207056.2:c.1944-2364G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_175849.2:c.2172-2364G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_006892.4:c.2292G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_175848.2:c.2232G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_175850.3:c.2268G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Immunodeficiency-centromeric instability-facial anomalies syndrome 1 (ICF1)
Identifiers:
MONDO: MONDO:0009454; MedGen: C4551557; Orphanet: 2268; OMIM: 242860

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000914951Illumina Laboratory Services, Illumina
criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)		Uncertain significance
(Apr 28, 2017) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Clinical spectrum of immunodeficiency, centromeric instability and facial dysmorphism (ICF syndrome).

Hagleitner MM, Lankester A, Maraschio P, Hultén M, Fryns JP, Schuetz C, Gimelli G, Davies EG, Gennery A, Belohradsky BH, de Groot R, Gerritsen EJ, Mattina T, Howard PJ, Fasth A, Reisli I, Furthner D, Slatter MA, Cant AJ, Cazzola G, van Dijken PJ, van Deuren M, et al.

J Med Genet. 2008 Feb;45(2):93-9. Epub 2007 Sep 24.

PubMed [citation]
PMID:
17893117

Heterogeneous clinical presentation in ICF syndrome: correlation with underlying gene defects.

Weemaes CM, van Tol MJ, Wang J, van Ostaijen-ten Dam MM, van Eggermond MC, Thijssen PE, Aytekin C, Brunetti-Pierri N, van der Burg M, Graham Davies E, Ferster A, Furthner D, Gimelli G, Gennery A, Kloeckener-Gruissem B, Meyn S, Powell C, Reisli I, Schuetz C, Schulz A, Shugar A, van den Elsen PJ, et al.

Eur J Hum Genet. 2013 Nov;21(11):1219-25. doi: 10.1038/ejhg.2013.40. Epub 2013 Mar 13.

PubMed [citation]
PMID:
23486536
PMCID:
PMC3798845

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000914951.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The DNMT3B c.2292G>T (p.Arg764Ser) variant has been reported in a compound heterozygous state with a frameshift variant in one patient with immunodeficiency-centromeric instability-facial anomalies syndrome (Hagleitner et al. 2008; Weemaes et al. 2013). Control data are unavailable for this variant, which is reported at a frequency of 0.00004 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional data using isolated T-lymphocytes from the patient carrying the p.Arg764Ser variant show that the T-cell expansion was significantly reduced compared to unrelated controls (Weemaes et al. 2013). The evidence for this variant is limited. The p.Arg764Ser variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for immunodeficiency-centromeric instability-facial anomalies syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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

Last Updated: Sep 29, 2024