U.S. flag

An official website of the United States government

NM_031844.3(HNRNPU):c.803+2T>C AND Developmental and epileptic encephalopathy, 54

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Mar 11, 2020
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:
RCV002550961.9

Allele description [Variation Report for NM_031844.3(HNRNPU):c.803+2T>C]

NM_031844.3(HNRNPU):c.803+2T>C

Gene:
HNRNPU:heterogeneous nuclear ribonucleoprotein U [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q44
Genomic location:
Preferred name:
NM_031844.3(HNRNPU):c.803+2T>C
HGVS:
  • NC_000001.11:g.244862617A>G
  • NG_042184.1:g.6909T>C
  • NM_004501.3:c.746+2T>C
  • NM_031844.3:c.803+2T>CMANE SELECT
  • NC_000001.10:g.245025919A>G
Links:
dbSNP: rs112081356
NCBI 1000 Genomes Browser:
rs112081356
Molecular consequence:
  • NM_004501.3:c.746+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_031844.3:c.803+2T>C - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 54
Synonyms:
Epileptic encephalopathy, early infantile, 54
Identifiers:
MONDO: MONDO:0033363; MedGen: C4479319; OMIM: 617391

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001575528Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Mar 11, 2020)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]
PMID:
16199547
PMCID:
PMC1735933

Molecular characterization of 1q44 microdeletion in 11 patients reveals three candidate genes for intellectual disability and seizures.

Thierry G, Bénéteau C, Pichon O, Flori E, Isidor B, Popelard F, Delrue MA, Duboscq-Bidot L, Thuresson AC, van Bon BW, Cailley D, Rooryck C, Paubel A, Metay C, Dusser A, Pasquier L, Béri M, Bonnet C, Jaillard S, Dubourg C, Tou B, Quéré MP, et al.

Am J Med Genet A. 2012 Jul;158A(7):1633-40. doi: 10.1002/ajmg.a.35423. Epub 2012 Jun 7.

PubMed [citation]
PMID:
22678713
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001575528.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in HNRNPU are known to be pathogenic (PMID: 22678713, 28283832). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with HNRNPU-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 2 of the HNRNPU gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product.

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

Last Updated: Apr 20, 2024