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]

Link to SEPIO compliant JSON-LD document

Variant: NM_001033855.3(DCLRE1C):c.526A>G (p.Ile176Val)

CA5416811

288327 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 40260efd-1325-44d5-8d14-32c42b5c2292

Approved on: 2024-06-13

Published on: 2024-06-13

HGVS expressions

NM_001033855.3:c.526A>G

NM_001033855.3(DCLRE1C):c.526A>G (p.Ile176Val)

NC_000010.11:g.14934714T>C

CM000672.2:g.14934714T>C

NC_000010.10:g.14976713T>C

CM000672.1:g.14976713T>C

NC_000010.9:g.15016719T>C

NG_007276.1:g.24382A>G

ENST00000378241.6:c.*573A>G

ENST00000456122.2:c.*712A>G

ENST00000489161.2:c.*304A>G

ENST00000492201.6:c.526A>G

ENST00000697047.1:c.526A>G

ENST00000697070.1:c.526A>G

ENST00000697071.1:c.*446A>G

ENST00000697072.1:c.526A>G

ENST00000697073.1:c.*304A>G

ENST00000697074.1:c.*304A>G

ENST00000697075.1:c.526A>G

ENST00000697076.1:c.526A>G

ENST00000697077.1:c.*237A>G

ENST00000697078.1:c.*233A>G

ENST00000697079.1:n.230A>G

ENST00000697080.1:c.*390A>G

ENST00000697081.1:c.*143A>G

ENST00000697082.1:c.*712A>G

ENST00000697083.1:c.*386A>G

ENST00000697084.1:c.526A>G

ENST00000697085.1:c.*293A>G

ENST00000697086.1:n.2963A>G

ENST00000697087.1:c.*446A>G

ENST00000697088.1:c.*143A>G

ENST00000697089.1:c.*446A>G

ENST00000697090.1:n.534A>G

ENST00000378278.7:c.526A>G

ENST00000357717.6:c.181A>G

ENST00000378241.5:c.166A>G

ENST00000378246.6:c.181A>G

ENST00000378249.5:c.181A>G

ENST00000378254.5:c.166A>G

ENST00000378255.5:c.166A>G

ENST00000378258.5:c.166A>G

ENST00000378278.6:c.526A>G

ENST00000378289.8:c.526A>G

ENST00000396817.6:c.166A>G

ENST00000418843.5:c.88A>G

NM_001033855.2:c.526A>G

NM_001033857.2:c.166A>G

NM_001033858.2:c.166A>G

NM_001289076.1:c.181A>G

NM_001289077.1:c.166A>G

NM_001289078.1:c.181A>G

NM_001289079.1:c.166A>G

NM_022487.3:c.181A>G

NR_110297.1:n.1160A>G

NM_001350965.1:c.526A>G

NM_001350966.1:c.181A>G

NM_001350967.1:c.166A>G

NR_146960.1:n.948A>G

NR_146961.1:n.977A>G

NR_146962.1:n.948A>G

NM_001033857.3:c.166A>G

NM_001033858.3:c.166A>G

NM_001289076.2:c.181A>G

NM_001289077.2:c.166A>G

NM_001289078.2:c.181A>G

NM_001289079.2:c.166A>G

NM_001350965.2:c.526A>G

NM_001350966.2:c.181A>G

NM_001350967.2:c.166A>G

NM_022487.4:c.181A>G

NR_110297.2:n.824A>G

NR_146961.2:n.641A>G

Uncertain Significance

PM2 BA1 BS1 BS2

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.526A>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Isoleucine by Valine at amino acid 176 (p.Ile176Val). The filtering allele frequency (the upper threshold of the 95% CI of 15/75028 alleles) of the c.526A>G variant in DCLRE1C is 0.0001227 for African/African American chromosomes by gnomAD v4, which is lower than the SCID-VCEP threshold for BS1 (>0.00078) and BA1 (>0.00346) but higher than the threshold (<0.00003266) for PM2_Supporting (BS1 not met, BA1 not met, PM2_Supporting not met). No homozygotes have been observed in gnomAD. To our knowledge, this variant has not been reported in the literature in individuals affected with SCID/DCLRE1C-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): No criteria were applied.

PM2

The filtering allele frequency (the upper threshold of the 95% CI of 15/75028 alleles) of the c.526A>G variant in DCLRE1C is 0.0001227 for African/African American chromosomes by gnomAD v4, which is lower than the SCID-VCEP threshold for BS1 (>0.00078) and BA1 (>0.00346) but higher than the threshold (<0.00003266) for PM2_Supporting (BS1 not met, BA1 not met, PM2_Supporting not met).

BA1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

BS2

No homozygotes have been observed in gnomAD.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.