Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

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Variant: NM_001033855.3(DCLRE1C):c.161+2T>G

CA376064378

1722324 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e3abe4b3-129d-45a5-aae6-2d0fdce43b67

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_001033855.3:c.161+2T>G

NM_001033855.3(DCLRE1C):c.161+2T>G

NC_000010.11:g.14949034A>C

CM000672.2:g.14949034A>C

NC_000010.10:g.14991033A>C

CM000672.1:g.14991033A>C

NC_000010.9:g.15031039A>C

NG_007276.1:g.10062T>G

ENST00000378278.7:c.161+2T>G

ENST00000357717.6:c.-44+2T>G

ENST00000378241.5:c.-412+2T>G

ENST00000378246.6:c.-129+2T>G

ENST00000378249.5:c.-128-3845T>G

ENST00000378254.5:c.-331+2T>G

ENST00000378255.5:c.-653+2T>G

ENST00000378258.5:c.-285+2T>G

ENST00000378278.6:c.161+2T>G

ENST00000378289.8:c.161+2T>G

ENST00000396817.6:c.-607+2T>G

ENST00000418843.5:c.-368+2T>G

ENST00000456122.1:c.-536+2T>G

NM_001033855.2:c.161+2T>G

NM_001033857.2:c.-285+2T>G

NM_001033858.2:c.-607+2T>G

NM_001289076.1:c.-44+2T>G

NM_001289077.1:c.-331+2T>G

NM_001289078.1:c.-128-3845T>G

NM_001289079.1:c.-653+2T>G

NM_022487.3:c.-129+2T>G

NR_110297.1:n.583+2T>G

NM_001350965.1:c.161+2T>G

NM_001350966.1:c.-128-3845T>G

NM_001350967.1:c.-285+2T>G

NR_146960.1:n.583+2T>G

NR_146961.1:n.583+2T>G

NR_146962.1:n.583+2T>G

NM_001033857.3:c.-285+2T>G

NM_001033858.3:c.-607+2T>G

NM_001289076.2:c.-44+2T>G

NM_001289077.2:c.-331+2T>G

NM_001289078.2:c.-128-3845T>G

NM_001289079.2:c.-653+2T>G

NM_001350965.2:c.161+2T>G

NM_001350966.2:c.-128-3845T>G

NM_001350967.2:c.-285+2T>G

NM_022487.4:c.-129+2T>G

NR_110297.2:n.247+2T>G

NR_146961.2:n.247+2T>G

Pathogenic

PM3_Supporting PP4_Moderate PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for DCLRE1C Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The c.161+2T>G (NM_001033855.3) variant in DCLRE1C occurs within the canonical splice donor site (+2) of intron 2. It is predicted to cause skipping of a biologically relevant exon, resulting in a frameshift leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1 is met). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). Although patients carrying this variant have not been published in the literature, there is one ClinVar entry from Cowan and Puck Lab, Allergy Immunology and BMT Division, UCSF Benioff Children's Hospital Accession: SCV002598533.1. By internal communication, 0.5 pts for the information that the patient is homozygous. PM3_Suppoting. The patient presented: * Vector-based complementation corrected increased cellular radiosensitivity and/or decreased V(D)J recombination: 2 points, PP4_Moderate. In summary, this variant meets the criteria to be classified as a Pathogenic for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PVS1, PM2_Supporting, PM3_Supporting, and PP4_Moderate (VCEP specifications version 1).

PM3_Supporting

Although patients carrying this variant have not been published in the literature, there is one ClinVar entry from Cowan and Puck Lab, Allergy Immunology and BMT Division, UCSF Benioff Children's Hospital Accession: SCV002598533.1. By internal communication, 0.5 pts for the information that the patient is homozygous. PM3_Suppoting.

PP4_Moderate

The patient presented: * Vector-based complementation corrected increased cellular radiosensitivity and/or decreased V(D)J recombination: 2 points, PP4_Moderate.

PVS1

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

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