NM_001033855.3(DCLRE1C):c.457G>A (p.Gly153Arg) AND not specified

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: Mar 9, 2018
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:: RCV000455778.19

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.457G>A (p.Gly153Arg)]

NM_001033855.3(DCLRE1C):c.457G>A (p.Gly153Arg)

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.457G>A (p.Gly153Arg)

Other names:

NM_001033855.3(DCLRE1C):c.457G>A

HGVS:

NC_000010.11:g.14935470C>T
NG_007276.1:g.23626G>A
NM_001033855.3:c.457G>AMANE SELECT
NM_001033857.3:c.97G>A
NM_001033858.3:c.97G>A
NM_001289076.2:c.112G>A
NM_001289077.2:c.97G>A
NM_001289078.2:c.112G>A
NM_001289079.2:c.97G>A
NM_001350965.2:c.457G>A
NM_001350966.2:c.112G>A
NM_001350967.2:c.97G>A
NM_022487.4:c.112G>A
NP_001029027.1:p.Gly153Arg
NP_001029029.1:p.Gly33Arg
NP_001029030.1:p.Gly33Arg
NP_001276005.1:p.Gly38Arg
NP_001276006.1:p.Gly33Arg
NP_001276007.1:p.Gly38Arg
NP_001276008.1:p.Gly33Arg
NP_001337894.1:p.Gly153Arg
NP_001337895.1:p.Gly38Arg
NP_001337896.1:p.Gly33Arg
NP_071932.2:p.Gly38Arg
LRG_54t1:c.457G>A
LRG_54:g.23626G>A
NC_000010.10:g.14977469C>T
NM_001033855.1:c.457G>A
NM_001033855.2:c.457G>A
NM_001033857.1:c.97G>A
NM_001033858.1:c.97G>A
NR_110297.2:n.755G>A
NR_146960.1:n.879G>A
NR_146961.2:n.572G>A
NR_146962.1:n.879G>A

Protein change:

G153R

Links:

dbSNP: rs41297018

NCBI 1000 Genomes Browser:

rs41297018

Molecular consequence:

NM_001033855.3:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033857.3:c.97G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001033858.3:c.97G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289076.2:c.112G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289077.2:c.97G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289078.2:c.112G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001289079.2:c.97G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350965.2:c.457G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350966.2:c.112G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001350967.2:c.97G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_022487.4:c.112G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_110297.2:n.755G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146960.1:n.879G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146961.2:n.572G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146962.1:n.879G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000052308	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Mar 9, 2018)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25917813, 18223550 Citation Link,
SCV000538776	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Mar 28, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000720401	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Jan 20, 2017)	germline	clinical testing	Citation Link,
SCV001742669	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Benign	germline	clinical testing

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

Functional analysis of naturally occurring DCLRE1C mutations and correlation with the clinical phenotype of ARTEMIS deficiency.

Felgentreff K, Lee YN, Frugoni F, Du L, van der Burg M, Giliani S, Tezcan I, Reisli I, Mejstrikova E, de Villartay JP, Sleckman BP, Manis J, Notarangelo LD.

J Allergy Clin Immunol. 2015 Jul;136(1):140-150.e7. doi: 10.1016/j.jaci.2015.03.005. Epub 2015 Apr 25.

PubMed [citation]

PMID:: 25917813
PMCID:: PMC4494888

Restoration of human B-cell differentiation into NOD-SCID mice engrafted with gene-corrected CD34+ cells isolated from Artemis or RAG1-deficient patients.

Lagresle-Peyrou C, Benjelloun F, Hue C, Andre-Schmutz I, Bonhomme D, Forveille M, Beldjord K, Hacein-Bey-Abina S, De Villartay JP, Charneau P, Durandy A, Fischer A, Cavazzana-Calvo M.

Mol Ther. 2008 Feb;16(2):396-403. doi: 10.1038/sj.mt.6300353. Epub 2007 Nov 27.

PubMed [citation]

PMID:: 18223550

See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000052308.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: DCLRE1C c.457G>A (p.Gly153Arg) results in a non-conservative amino acid change located in the Metallo-beta-lactamase domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.011 in 120654 control chromosomes in the ExAC database, including 12 homozygotes. The observed variant frequency is approximately 2.72 fold of the estimated maximal expected allele frequency for a pathogenic variant in DCLRE1C causing Severe Combined Immunodeficiency Syndrome phenotype (0.0041), strongly suggesting that the variant is benign. c.457G>A has been reported in the literature in individuals affected with Severe Combined Immunodeficiency Syndrome. These report(s) do not provide unequivocal conclusions about association of the variant with Severe Combined Immunodeficiency Syndrome. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was 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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000538776.1

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

Description

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Variant associated with SCID, but high frequency and a functional study suggests no impact on activity.

#	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 GeneDx, SCV000720401.1

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001742669.3

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

#	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: Apr 20, 2024

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