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NM_001033855.3(DCLRE1C):c.1315G>T (p.Glu439Ter) AND Severe combined immunodeficiency due to DCLRE1C deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 15, 2019
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:
RCV001223880.7

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.1315G>T (p.Glu439Ter)]

NM_001033855.3(DCLRE1C):c.1315G>T (p.Glu439Ter)

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.1315G>T (p.Glu439Ter)
HGVS:
  • NC_000010.11:g.14909172C>A
  • NG_007276.1:g.49924G>T
  • NM_001033855.3:c.1315G>TMANE SELECT
  • NM_001033857.3:c.955G>T
  • NM_001033858.3:c.955G>T
  • NM_001289076.2:c.970G>T
  • NM_001289077.2:c.955G>T
  • NM_001289078.2:c.970G>T
  • NM_001289079.2:c.955G>T
  • NM_001350965.2:c.1315G>T
  • NM_001350966.2:c.970G>T
  • NM_001350967.2:c.955G>T
  • NM_022487.4:c.970G>T
  • NP_001029027.1:p.Glu439Ter
  • NP_001029029.1:p.Glu319Ter
  • NP_001029030.1:p.Glu319Ter
  • NP_001276005.1:p.Glu324Ter
  • NP_001276006.1:p.Glu319Ter
  • NP_001276007.1:p.Glu324Ter
  • NP_001276008.1:p.Glu319Ter
  • NP_001337894.1:p.Glu439Ter
  • NP_001337895.1:p.Glu324Ter
  • NP_001337896.1:p.Glu319Ter
  • NP_071932.2:p.Glu324Ter
  • LRG_54:g.49924G>T
  • NC_000010.10:g.14951171C>A
  • NM_001033855.2:c.1315G>T
  • NR_110297.2:n.1754G>T
  • NR_146960.1:n.1682G>T
  • NR_146961.2:n.1495G>T
  • NR_146962.1:n.1802G>T
Protein change:
E319*
Links:
dbSNP: rs753674918
NCBI 1000 Genomes Browser:
rs753674918
Molecular consequence:
  • NR_110297.2:n.1754G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146960.1:n.1682G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146961.2:n.1495G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146962.1:n.1802G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001033855.3:c.1315G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001033857.3:c.955G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001033858.3:c.955G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001289076.2:c.970G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001289077.2:c.955G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001289078.2:c.970G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001289079.2:c.955G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350965.2:c.1315G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350966.2:c.970G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001350967.2:c.955G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_022487.4:c.970G>T - nonsense - [Sequence Ontology: SO:0001587]

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001396048Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 15, 2019) 		germlineclinical testing

PubMed (5)
[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

Partial T and B lymphocyte immunodeficiency and predisposition to lymphoma in patients with hypomorphic mutations in Artemis.

Moshous D, Pannetier C, Chasseval Rd Rd, Deist Fl Fl, Cavazzana-Calvo M, Romana S, Macintyre E, Canioni D, Brousse N, Fischer A, Casanova JL, Villartay JP.

J Clin Invest. 2003 Feb;111(3):381-7.

PubMed [citation]
PMID:
12569164
PMCID:
PMC151863

The most frequent DCLRE1C (ARTEMIS) mutations are based on homologous recombination events.

Pannicke U, Hönig M, Schulze I, Rohr J, Heinz GA, Braun S, Janz I, Rump EM, Seidel MG, Matthes-Martin S, Soerensen J, Greil J, Stachel DK, Belohradsky BH, Albert MH, Schulz A, Ehl S, Friedrich W, Schwarz K.

Hum Mutat. 2010 Feb;31(2):197-207. doi: 10.1002/humu.21168.

PubMed [citation]
PMID:
19953608
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001396048.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the DCLRE1C protein. Other variant(s) that disrupt this region (p.Asp451Lysfs*11) have been determined to be pathogenic (PMID: 12569164, 19953608, 21147755, 25917813). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has not been reported in the literature in individuals with DCLRE1C-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the DCLRE1C gene (p.Glu439*). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 254 amino acids of the DCLRE1C protein.

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

Last Updated: Feb 28, 2024