NM_001033855.3(DCLRE1C):c.1978_1981dup (p.Leu661Ter) AND Severe combined immunodeficiency due to DCLRE1C deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 2, 2024
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:: RCV003827146.2

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.1978_1981dup (p.Leu661Ter)]

NM_001033855.3(DCLRE1C):c.1978_1981dup (p.Leu661Ter)

Gene:

DCLRE1C:DNA cross-link repair 1C [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

10p13

Genomic location:

Preferred name:

NM_001033855.3(DCLRE1C):c.1978_1981dup (p.Leu661Ter)

HGVS:

NC_000010.11:g.14908507_14908510dup
NG_007276.1:g.50587_50590dup
NM_001033855.3:c.1978_1981dupMANE SELECT
NM_001033857.3:c.1618_1621dup
NM_001033858.3:c.1618_1621dup
NM_001289076.2:c.1633_1636dup
NM_001289077.2:c.1618_1621dup
NM_001289078.2:c.1633_1636dup
NM_001289079.2:c.1618_1621dup
NM_001350965.2:c.1782+196_1782+199dup
NM_001350966.2:c.1437+196_1437+199dup
NM_001350967.2:c.1422+196_1422+199dup
NM_022487.4:c.1633_1636dup
NP_001029027.1:p.Leu661Ter
NP_001029027.1:p.Leu661Terfs
NP_001029029.1:p.Leu541Ter
NP_001029030.1:p.Leu541Ter
NP_001276005.1:p.Leu546Ter
NP_001276006.1:p.Leu541Ter
NP_001276007.1:p.Leu546Ter
NP_001276008.1:p.Leu541Ter
NP_071932.2:p.Leu546Ter
LRG_54t1:c.1977_1980dup
LRG_54:g.50587_50590dup
LRG_54p1:p.Leu661Terfs
NC_000010.10:g.14950504_14950505insACTC
NC_000010.10:g.14950506_14950509dup
NM_001033855.1:c.1977_1980dup
NR_110297.2:n.2417_2420dup
NR_146961.2:n.2158_2161dup
NR_146962.1:n.2465_2468dup

Protein change:

L541*

Molecular consequence:

NM_001350965.2:c.1782+196_1782+199dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001350966.2:c.1437+196_1437+199dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001350967.2:c.1422+196_1422+199dup - intron variant - [Sequence Ontology: SO:0001627]
NR_110297.2:n.2417_2420dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146961.2:n.2158_2161dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146962.1:n.2465_2468dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001033855.3:c.1978_1981dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001033857.3:c.1618_1621dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001033858.3:c.1618_1621dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001289076.2:c.1633_1636dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001289077.2:c.1618_1621dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001289078.2:c.1633_1636dup - nonsense - [Sequence Ontology: SO:0001587]
NM_001289079.2:c.1618_1621dup - nonsense - [Sequence Ontology: SO:0001587]
NM_022487.4:c.1633_1636dup - nonsense - [Sequence Ontology: SO:0001587]

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

Recent activity

Clear Turn Off Turn On

MULTISPECIES: LPS O-antigen chain length determinant protein WzzB [Enterobacteri...
MULTISPECIES: LPS O-antigen chain length determinant protein WzzB [Enterobacteriaceae]
gi|485777230|ref|WP_001400566.1|

Protein
Mus musculus transcription factor GATA-4 (Gata4) mRNA, complete cds
Mus musculus transcription factor GATA-4 (Gata4) mRNA, complete cds
gi|5882285|gb|AF179424.1|

Nucleotide
Mus musculus aldehyde dehydrogenase family 1, subfamily A3, mRNA (cDNA clone MGC...
Mus musculus aldehyde dehydrogenase family 1, subfamily A3, mRNA (cDNA clone MGC:67939 IMAGE:6515355), complete cds
gi|37194682|gb|BC058277.1|

Nucleotide
RNA-binding motif protein, Y chromosome, family 1 member A1 isoform 1 [Homo sapi...
RNA-binding motif protein, Y chromosome, family 1 member A1 isoform 1 [Homo sapiens]
gi|4826974|ref|NP_005049.1|

Protein
uncharacterized protein [Danio rerio]
uncharacterized protein [Danio rerio]
gi|2800588544|ref|XP_068077323.1|

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004628585	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 2, 2024)	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

SCV004628585

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 2, 2024)

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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004628585.1

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

Description

This sequence change creates a premature translational stop signal (p.Leu661*) in the DCLRE1C gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 32 amino acid(s) of the DCLRE1C protein. 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine