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NM_001033855.3(DCLRE1C):c.34C>T (p.Pro12Ser) AND Severe combined immunodeficiency due to DCLRE1C deficiency

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Apr 1, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV002957713.3

Allele description [Variation Report for NM_001033855.3(DCLRE1C):c.34C>T (p.Pro12Ser)]

NM_001033855.3(DCLRE1C):c.34C>T (p.Pro12Ser)

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.34C>T (p.Pro12Ser)
Other names:
NM_001033855.3(DCLRE1C):c.34C>T; p.Pro12Ser
HGVS:
  • NC_000010.11:g.14953977G>A
  • NG_007276.1:g.5119C>T
  • NG_118792.1:g.616G>A
  • NM_001033855.3:c.34C>TMANE SELECT
  • NM_001033857.3:c.-412C>T
  • NM_001033858.3:c.-734C>T
  • NM_001289076.2:c.-171C>T
  • NM_001289077.2:c.-458C>T
  • NM_001289078.2:c.-204C>T
  • NM_001289079.2:c.-780C>T
  • NM_001350965.2:c.34C>T
  • NM_001350966.2:c.-204C>T
  • NM_001350967.2:c.-412C>T
  • NM_022487.4:c.-256C>T
  • NP_001029027.1:p.Pro12Ser
  • NP_001029027.1:p.Pro12Ser
  • NP_001337894.1:p.Pro12Ser
  • LRG_54t1:c.34C>T
  • LRG_54:g.5119C>T
  • LRG_54p1:p.Pro12Ser
  • NC_000010.10:g.14995976G>A
  • NM_001033855.1:c.34C>T
  • NR_110297.2:n.120C>T
  • NR_146960.1:n.456C>T
  • NR_146961.2:n.120C>T
  • NR_146962.1:n.456C>T
Protein change:
P12S
Molecular consequence:
  • NM_001033857.3:c.-412C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001033858.3:c.-734C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289076.2:c.-171C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289077.2:c.-458C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289078.2:c.-204C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001289079.2:c.-780C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350966.2:c.-204C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001350967.2:c.-412C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_022487.4:c.-256C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001033855.3:c.34C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350965.2:c.34C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_110297.2:n.120C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146960.1:n.456C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146961.2:n.120C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146962.1:n.456C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003272596Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Mar 4, 2022) 		germlineclinical testing

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

SCV004810416ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen SCID ACMG Specifications DCLRE1C V1.0.0)		Uncertain significance
(Apr 1, 2024) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing, curation

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, SCV003272596.1

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

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 12 of the DCLRE1C protein (p.Pro12Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV004810416.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The c.34C>T (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Proline by Serine at amino acid 12 (p.Pro12Ser). This variant is absent from gnomAD v4 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with DCLRE1C-related conditions or in functional studies. In summary, this variant is classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency, based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): PM2_Supporting.

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

Last Updated: Sep 29, 2024