U.S. flag

An official website of the United States government

NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557fs) AND Severe combined immunodeficiency due to DCLRE1C deficiency

Germline classification:
Likely pathogenic (2 submissions)
Last evaluated:
Nov 14, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV000240842.2

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557fs)]

NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557fs)

Gene:
DCLRE1C:DNA cross-link repair 1C [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
10p13
Genomic location:
Preferred name:
NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557fs)
Other names:
NM_001033855.3(DCLRE1C):c.1669dup; p.Thr557fs
HGVS:
  • NC_000010.11:g.14908818dup
  • NG_007276.1:g.50278dup
  • NM_001033855.3:c.1669dupMANE SELECT
  • NM_001033857.3:c.1309dup
  • NM_001033858.3:c.1309dup
  • NM_001289076.2:c.1324dup
  • NM_001289077.2:c.1309dup
  • NM_001289078.2:c.1324dup
  • NM_001289079.2:c.1309dup
  • NM_001350965.2:c.1669dup
  • NM_001350966.2:c.1324dup
  • NM_001350967.2:c.1309dup
  • NM_022487.4:c.1324dup
  • NP_001029027.1:p.Thr557fs
  • NP_001029029.1:p.Thr437fs
  • NP_001029030.1:p.Thr437fs
  • NP_001276005.1:p.Thr442fs
  • NP_001276006.1:p.Thr437fs
  • NP_001276007.1:p.Thr442fs
  • NP_001276008.1:p.Thr437fs
  • NP_001337894.1:p.Thr557fs
  • NP_001337895.1:p.Thr442fs
  • NP_001337896.1:p.Thr437fs
  • NP_071932.2:p.Thr442fs
  • LRG_54t1:c.1669_1670insA
  • LRG_54:g.50278dup
  • NC_000010.10:g.14950817dup
  • NM_001033855.1:c.1669_1670insA
  • NR_110297.2:n.2108dup
  • NR_146960.1:n.2036dup
  • NR_146961.2:n.1849dup
  • NR_146962.1:n.2156dup
Protein change:
T437fs
Links:
OMIM: 605988.0015; dbSNP: rs886037924
NCBI 1000 Genomes Browser:
rs886037924
Molecular consequence:
  • NM_001033855.3:c.1669dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001033857.3:c.1309dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001033858.3:c.1309dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289076.2:c.1324dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289077.2:c.1309dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289078.2:c.1324dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001289079.2:c.1309dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350965.2:c.1669dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350966.2:c.1324dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350967.2:c.1309dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_022487.4:c.1324dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_110297.2:n.2108dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146960.1:n.2036dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146961.2:n.1849dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146962.1:n.2156dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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

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
SCV000299329OMIM
no assertion criteria provided
Pathogenic
(Sep 14, 2016)
germlineliterature only

PubMed (1)
[See all records that cite this PMID]

SCV004102779ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen SCID ACMG Specifications DCLRE1C V1.0.0)
Likely pathogenic
(Nov 14, 2023)
germlinecuration

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

DCLRE1C (ARTEMIS) mutations causing phenotypes ranging from atypical severe combined immunodeficiency to mere antibody deficiency.

Volk T, Pannicke U, Reisli I, Bulashevska A, Ritter J, Björkman A, Schäffer AA, Fliegauf M, Sayar EH, Salzer U, Fisch P, Pfeifer D, Di Virgilio M, Cao H, Yang F, Zimmermann K, Keles S, Caliskaner Z, Güner SÜ, Schindler D, Hammarström L, Rizzi M, et al.

Hum Mol Genet. 2015 Dec 20;24(25):7361-72. doi: 10.1093/hmg/ddv437. Epub 2015 Oct 16.

PubMed [citation]
PMID:
26476407
PMCID:
PMC4664172

Details of each submission

From OMIM, SCV000299329.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (1)

Description

For discussion of the 1-bp insertion (c.1669_1670insA, NM_001033855.1) in exon 14 of the DCLRE1C gene, resulting in a frameshift and premature termination (Thr577AsnfsTer21), that was found in compound heterozygous state in 2 sibs with severe combined immunodeficiency with sensitivity to ionizing radiation (RS-SCID; 602450) by Volk et al. (2015), see 605988.0014.

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

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV004102779.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The NM_001033855.3(DCLRE1C):c.1669dup (p.Thr557AsnfsTer21) variant in DCLRE1C is a frameshift variant that may cause loss of function of the protein; however, it is predicted that the transcript likely escapes nonsense-mediated decay (PMID: 26476407 supports this notion). Additionally, no downstream pathogenic variants have been curated to date (curated following SCID VCEP specifications). Thus, currently, this variant is limited to PVS1 at moderate strength. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). There are 2 patients who are siblings (Family A, P4, and P5) (PMID: 26476407, PP1_supporting). At least one patient with this variant displayed Vector-based complementation corrected increased cellular radiosensitivity and/or decreased V(D)J recombination (P5, 2 pts, PMID:26476407, PP4_Moderate). In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive SCID based on the ACMG/AMP criteria applied: PVS1_Moderate, PM2_Supporting, PP1_Supporting, and PP4_Moderate, as specified by the ClinGen SCID VCEP (VCEP specifications version 1).

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

Last Updated: Nov 25, 2023