U.S. flag

An official website of the United States government

NM_001033855.3(DCLRE1C):c.678+2T>G AND Severe combined immunodeficiency due to DCLRE1C deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 9, 2023
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:
RCV003856886.1

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.678+2T>G]

NM_001033855.3(DCLRE1C):c.678+2T>G

Gene:
DCLRE1C:DNA cross-link repair 1C [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_001033855.3(DCLRE1C):c.678+2T>G
HGVS:
  • NC_000010.11:g.14934378A>C
  • NG_007276.1:g.24718T>G
  • NM_001033855.3:c.678+2T>GMANE SELECT
  • NM_001033857.3:c.318+2T>G
  • NM_001033858.3:c.318+2T>G
  • NM_001289076.2:c.333+2T>G
  • NM_001289077.2:c.318+2T>G
  • NM_001289078.2:c.333+2T>G
  • NM_001289079.2:c.318+2T>G
  • NM_001350965.2:c.678+2T>G
  • NM_001350966.2:c.333+2T>G
  • NM_001350967.2:c.318+2T>G
  • NM_022487.4:c.333+2T>G
  • LRG_54:g.24718T>G
  • NC_000010.10:g.14976377A>C
Molecular consequence:
  • NM_001033855.3:c.678+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001033857.3:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001033858.3:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001289076.2:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001289077.2:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001289078.2:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001289079.2:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001350965.2:c.678+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001350966.2:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_001350967.2:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
  • NM_022487.4:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

Name:
Severe combined immunodeficiency due to DCLRE1C deficiency (RS-SCID)
Synonyms:
Severe combined immunodeficiency with sensitivity to ionizing radiation; SCID, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE, WITH SENSITIVITY TO IONIZING RADIATION
Identifiers:
MONDO: MONDO:0011225; MedGen: C1865370; Orphanet: 275; OMIM: 602450

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004658898Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Dec 9, 2023) 		germlineclinical testing

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

Help

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

Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency.

Felgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, Avcin T, Qasim W, Davies EG, Niehues T, Ehl S.

Clin Immunol. 2011 Oct;141(1):73-82. doi: 10.1016/j.clim.2011.05.007. Epub 2011 May 30. Review.

PubMed [citation]
PMID:
21664875
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004658898.1

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

Description

This sequence change affects a donor splice site in intron 8 of the DCLRE1C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

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

Last Updated: Jun 17, 2024