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]

Variant: NM_001033855.3(DCLRE1C):c.227G>C (p.Arg76Thr)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA5416971

379076 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d4696620-30cd-4692-9933-4e11fc4e5158

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_001033855.3:c.227G>C

NM_001033855.3(DCLRE1C):c.227G>C (p.Arg76Thr)

NC_000010.11:g.14945124C>G

CM000672.2:g.14945124C>G

NC_000010.10:g.14987123C>G

CM000672.1:g.14987123C>G

NC_000010.9:g.15027129C>G

NG_007276.1:g.13972G>C

ENST00000378278.7:c.227G>C

ENST00000357717.6:c.-44+3912G>C

ENST00000378241.5:c.-261G>C

ENST00000378246.6:c.-63G>C

ENST00000378249.5:c.-63G>C

ENST00000378254.5:c.-134G>C

ENST00000378255.5:c.-456G>C

ENST00000378258.5:c.-134G>C

ENST00000378278.6:c.227G>C

ENST00000378289.8:c.227G>C

ENST00000396817.6:c.-456G>C

ENST00000418843.5:c.-171G>C

ENST00000456122.1:c.-385G>C

NM_001033855.2:c.227G>C

NM_001033857.2:c.-134G>C

NM_001033858.2:c.-456G>C

NM_001289076.1:c.-44+3912G>C

NM_001289077.1:c.-134G>C

NM_001289078.1:c.-63G>C

NM_001289079.1:c.-456G>C

NM_022487.3:c.-63G>C

NR_110297.1:n.734G>C

NM_001350965.1:c.227G>C

NM_001350966.1:c.-63G>C

NM_001350967.1:c.-134G>C

NR_146960.1:n.649G>C

NR_146961.1:n.734G>C

NR_146962.1:n.649G>C

NM_001033857.3:c.-134G>C

NM_001033858.3:c.-456G>C

NM_001289076.2:c.-44+3912G>C

NM_001289077.2:c.-134G>C

NM_001289078.2:c.-63G>C

NM_001289079.2:c.-456G>C

NM_001350965.2:c.227G>C

NM_001350966.2:c.-63G>C

NM_001350967.2:c.-134G>C

NM_022487.4:c.-63G>C

NR_110297.2:n.398G>C

NR_146961.2:n.398G>C

Benign

BA1

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.227G>C (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Arginine by Threonine at amino acid 76 p.Arg76Thr. The filtering allele frequency (the lower threshold of the 95% CI of 713/24912) of the c.227G>C variant in DCLRE1C is 0.02613 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Additionally, there have been descriptions of 11 homozygous individuals. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BA1. (VCEP specifications version 1).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 713/24912) of the c.227G>C variant in DCLRE1C is 0.02613 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Furthermore, there have been descriptions of 11 individuals who are homozygous.

Curation History

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