NM_206937.2(LIG4):c.26C>T (p.Thr9Ile) AND DNA ligase IV deficiency

Germline classification:: Benign (3 submissions)
Last evaluated:: Feb 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000325082.15

Allele description [Variation Report for NM_206937.2(LIG4):c.26C>T (p.Thr9Ile)]

NM_206937.2(LIG4):c.26C>T (p.Thr9Ile)

Gene:

LIG4:DNA ligase 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

13q33.3

Genomic location:

Preferred name:

NM_206937.2(LIG4):c.26C>T (p.Thr9Ile)

Other names:

p.T9I:ACT>ATT

HGVS:

NC_000013.11:g.108211243G>A
NG_007396.1:g.9292C>T
NM_001098268.2:c.26C>T
NM_001330595.2:c.-149-27C>T
NM_001352598.2:c.26C>T
NM_001352599.2:c.26C>T
NM_001352600.2:c.26C>T
NM_001352601.2:c.26C>T
NM_001352602.2:c.26C>T
NM_001352603.1:c.26C>T
NM_001352604.2:c.89-27C>T
NM_001379095.1:c.26C>T
NM_002312.3:c.26C>T
NM_206937.2:c.26C>TMANE SELECT
NP_001091738.1:p.Thr9Ile
NP_001339527.1:p.Thr9Ile
NP_001339528.1:p.Thr9Ile
NP_001339529.1:p.Thr9Ile
NP_001339530.1:p.Thr9Ile
NP_001339531.1:p.Thr9Ile
NP_001339532.1:p.Thr9Ile
NP_001366024.1:p.Thr9Ile
NP_002303.2:p.Thr9Ile
NP_996820.1:p.Thr9Ile
LRG_79t1:c.26C>T
LRG_79:g.9292C>T
LRG_79p1:p.Thr9Ile
NC_000013.10:g.108863591G>A
NM_206937.1:c.26C>T
P49917:p.Thr9Ile

Protein change:

T9I; THR9ILE

Links:

UniProtKB: P49917#VAR_033884; OMIM: 601837.0006; dbSNP: rs1805388

NCBI 1000 Genomes Browser:

rs1805388

Molecular consequence:

NM_001330595.2:c.-149-27C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001352604.2:c.89-27C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001098268.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352598.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352599.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352600.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352601.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352602.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001352603.1:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379095.1:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_002312.3:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_206937.2:c.26C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000382236	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Apr 27, 2017)	germline	clinical testing	Citation Link,
SCV001000324	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 1, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004015809	KCCC/NGS Laboratory, Kuwait Cancer Control Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign (Jul 7, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000382236

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Apr 27, 2017)

germline

clinical testing

Citation Link,

SCV001000324

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Feb 1, 2024)

germline

clinical testing

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

SCV004015809

KCCC/NGS Laboratory, Kuwait Cancer Control Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Benign
(Jul 7, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000382236.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001000324.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From KCCC/NGS Laboratory, Kuwait Cancer Control Center, SCV004015809.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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