NM_002312.3(LIG4):c.2440C>T (p.Arg814Ter) AND Lig4 syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Pathogenic(1) (Last evaluated: Jul 7, 2014)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description

NM_002312.3(LIG4):c.2440C>T (p.Arg814Ter)

LIG4:DNA ligase 4 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_002312.3(LIG4):c.2440C>T (p.Arg814Ter)
  • NC_000013.11:g.108208829G>A
  • NG_007396.1:g.11706C>T
  • NM_001098268.1:c.2440C>T
  • NM_002312.3:c.2440C>T
  • NP_001091738.1:p.Arg814Ter
  • NP_002303.2:p.Arg814Ter
  • LRG_79t1:c.2440C>T
  • LRG_79:g.11706C>T
  • LRG_79p1:p.Arg814Ter
  • NC_000013.10:g.108861177G>A
  • p.Arg814*
Protein change:
R814*; ARG814TER
OMIM: 601837.0002; dbSNP: rs104894419
0.0002(A), 104894419
NCBI 1000 Genomes Browser:
Allele Frequency:
0.00008(A), GO-ESP
Molecular consequence:
  • NM_002312.3:c.2440C>T - nonsense - [Sequence Ontology: SO:0001587]


Lig4 syndrome
MedGen: C1847827; Orphanet: 99812; OMIM: 606593

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000028317OMIMno assertion criteria providedPathogenic
(Sep 1, 2005)
germlineliterature only

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

SCV000537725Genome Clinic of Geneva,University Hospital of Genevacriteria provided, single submitter
Likely pathogenic
(Jul 7, 2014)
paternalclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only
not providedpaternalyes3not providednot providednot providednot providedclinical testing



DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency.

O'Driscoll M, Cerosaletti KM, Girard PM, Dai Y, Stumm M, Kysela B, Hirsch B, Gennery A, Palmer SE, Seidel J, Gatti RA, Varon R, Oettinger MA, Neitzel H, Jeggo PA, Concannon P.

Mol Cell. 2001 Dec;8(6):1175-85.

PubMed [citation]

A patient with mutations in DNA Ligase IV: clinical features and overlap with Nijmegen breakage syndrome.

Ben-Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM.

Am J Med Genet A. 2005 Sep 1;137A(3):283-7.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000028317.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)


O'Driscoll et al. (2001) identified a 2440C-T transition of the LIG4 gene in 2 sibs (patients 2303 and 2304) with LIG4 syndrome (606593). The mutation resulted in an arg814-to-ter substitution (R814X). The patients were compound heterozygotes; the other allele had the R580X mutation (601837.0001). O'Driscoll et al. (2001) also identified the arg814-to-ter mutation in another patient with LIG4 syndrome (patient 99P0149) who was a compound heterozygote; the other LIG4 mutation in this patient was gly469 to glu (601837.0003).

In a 4-year-old boy with acute T-cell leukemia and a facial gestalt reminiscent of Nijmegen breakage syndrome, Ben-Omran et al. (2005) identified homozygosity for R814X in the LIG4 gene.

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

From Genome Clinic of Geneva,University Hospital of Geneva, SCV000537725.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (1)


This heterozygous variant in the LIG4 gene (autosomal recessive transmission) was identified in a twin pair (one male and one female patient) with extreme growth delay, who also harbours another variant in the LIG4 gene (compound heterozygosity)

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1paternalyesnot providednot providednot provided3not providednot providednot provided

Last Updated: Apr 27, 2018

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