NM_001033855.3(DCLRE1C):c.678+2T>G AND Severe combined immunodeficiency due to DCLRE1C deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Dec 9, 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:: RCV003856886.1

Allele description

NM_001033855.3(DCLRE1C):c.678+2T>G

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.678+2T>G

HGVS:

NC_000010.11:g.14934378A>C
NG_007276.1:g.24718T>G
NM_001033855.3:c.678+2T>GMANE SELECT
NM_001033857.3:c.318+2T>G
NM_001033858.3:c.318+2T>G
NM_001289076.2:c.333+2T>G
NM_001289077.2:c.318+2T>G
NM_001289078.2:c.333+2T>G
NM_001289079.2:c.318+2T>G
NM_001350965.2:c.678+2T>G
NM_001350966.2:c.333+2T>G
NM_001350967.2:c.318+2T>G
NM_022487.4:c.333+2T>G
LRG_54:g.24718T>G
NC_000010.10:g.14976377A>C

Molecular consequence:

NM_001033855.3:c.678+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001033857.3:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001033858.3:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001289076.2:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001289077.2:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001289078.2:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001289079.2:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350965.2:c.678+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350966.2:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_001350967.2:c.318+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]
NM_022487.4:c.333+2T>G - splice donor variant - [Sequence Ontology: SO:0001575]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004658898	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Dec 9, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 21664875, 26123418, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004658898

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Dec 9, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Clinical and immunological manifestations of patients with atypical severe combined immunodeficiency.

Felgentreff K, Perez-Becker R, Speckmann C, Schwarz K, Kalwak K, Markelj G, Avcin T, Qasim W, Davies EG, Niehues T, Ehl S.

Clin Immunol. 2011 Oct;141(1):73-82. doi: 10.1016/j.clim.2011.05.007. Epub 2011 May 30. Review.

PubMed [citation]

PMID:: 21664875

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV004658898.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects a donor splice site in intron 8 of the DCLRE1C gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DCLRE1C are known to be pathogenic (PMID: 21664875, 26123418). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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

Last Updated: Jun 17, 2024

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