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NM_206937.2(LIG4):c.2326del (p.Glu776fs) AND DNA ligase IV deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
May 22, 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:
RCV003620240.2

Allele description [Variation Report for NM_206937.2(LIG4):c.2326del (p.Glu776fs)]

NM_206937.2(LIG4):c.2326del (p.Glu776fs)

Gene:
LIG4:DNA ligase 4 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
13q33.3
Genomic location:
Preferred name:
NM_206937.2(LIG4):c.2326del (p.Glu776fs)
HGVS:
  • NC_000013.11:g.108208944del
  • NG_007396.1:g.11592del
  • NM_001098268.2:c.2326del
  • NM_001330595.2:c.2125del
  • NM_001352598.2:c.2326del
  • NM_001352599.2:c.2326del
  • NM_001352600.2:c.2326del
  • NM_001352601.2:c.2326del
  • NM_001352602.2:c.2326del
  • NM_001352603.1:c.2326del
  • NM_001352604.2:c.2362del
  • NM_001379095.1:c.2326del
  • NM_002312.3:c.2326del
  • NM_206937.2:c.2326delMANE SELECT
  • NP_001091738.1:p.Glu776fs
  • NP_001317524.1:p.Glu709fs
  • NP_001339527.1:p.Glu776fs
  • NP_001339528.1:p.Glu776fs
  • NP_001339529.1:p.Glu776fs
  • NP_001339530.1:p.Glu776fs
  • NP_001339531.1:p.Glu776fs
  • NP_001339532.1:p.Glu776fs
  • NP_001339533.1:p.Glu788fs
  • NP_001366024.1:p.Glu776fs
  • NP_002303.2:p.Glu776fs
  • NP_996820.1:p.Glu776fs
  • LRG_79t1:c.2326del
  • LRG_79:g.11592del
  • LRG_79p1:p.Glu776fs
  • NC_000013.10:g.108861291del
  • NC_000013.10:g.108861292del
Protein change:
E709fs
Molecular consequence:
  • NM_001098268.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001330595.2:c.2125del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352598.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352599.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352600.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352601.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352602.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352603.1:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001352604.2:c.2362del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001379095.1:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_002312.3:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_206937.2:c.2326del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
DNA ligase IV deficiency
Synonyms:
Lig4 syndrome
Identifiers:
MONDO: MONDO:0011686; MedGen: C1847827; Orphanet: 99812; OMIM: 606593

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004532544Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(May 22, 2023) 		germlineclinical testing

PubMed (2)
[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

Ligase-4 Deficiency Causes Distinctive Immune Abnormalities in Asymptomatic Individuals.

Felgentreff K, Baxi SN, Lee YN, Dobbs K, Henderson LA, Csomos K, Tsitsikov EN, Armanios M, Walter JE, Notarangelo LD.

J Clin Immunol. 2016 May;36(4):341-53. doi: 10.1007/s10875-016-0266-5. Epub 2016 Apr 11.

PubMed [citation]
PMID:
27063650
PMCID:
PMC4842108

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004532544.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the LIG4 protein in which other variant(s) (p.Arg814*) have been determined to be pathogenic (PMID: 27063650). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with LIG4-related conditions. This variant is present in population databases (rs757994549, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Glu776Lysfs*20) in the LIG4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 136 amino acid(s) of the LIG4 protein.

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

Last Updated: Sep 29, 2024