Evidence Repository
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.212C>T (p.Thr71Met)

CA5416976

536367 (ClinVar)

Gene: DCLRE1C
Condition: severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 4957b9ba-876e-4660-a80c-dc24b226ffc8
Approved on: 2024-02-15
Published on: 2024-02-15

HGVS expressions

NM_001033855.3:c.212C>T
NM_001033855.3(DCLRE1C):c.212C>T (p.Thr71Met)
NC_000010.11:g.14945139G>A
CM000672.2:g.14945139G>A
NC_000010.10:g.14987138G>A
CM000672.1:g.14987138G>A
NC_000010.9:g.15027144G>A
NG_007276.1:g.13957C>T
ENST00000378241.6:c.*132C>T
ENST00000456122.2:c.*132C>T
ENST00000489161.2:c.*46C>T
ENST00000492201.6:c.212C>T
ENST00000697047.1:c.212C>T
ENST00000697070.1:c.212C>T
ENST00000697071.1:c.*132C>T
ENST00000697072.1:c.212C>T
ENST00000697073.1:c.*46C>T
ENST00000697074.1:c.*46C>T
ENST00000697075.1:c.212C>T
ENST00000697076.1:c.212C>T
ENST00000697077.1:c.212C>T
ENST00000697078.1:c.212C>T
ENST00000697079.1:n.32C>T
ENST00000697080.1:c.*132C>T
ENST00000697081.1:c.212C>T
ENST00000697082.1:c.*132C>T
ENST00000697083.1:c.*132C>T
ENST00000697084.1:c.212C>T
ENST00000697085.1:c.212C>T
ENST00000697086.1:n.2649C>T
ENST00000697087.1:c.*132C>T
ENST00000697088.1:c.212C>T
ENST00000697089.1:c.*132C>T
ENST00000697090.1:n.220C>T
ENST00000697091.1:n.273C>T
ENST00000378278.7:c.212C>T
ENST00000357717.6:c.-44+3897C>T
ENST00000378241.5:c.-276C>T
ENST00000378246.6:c.-78C>T
ENST00000378249.5:c.-78C>T
ENST00000378254.5:c.-149C>T
ENST00000378255.5:c.-471C>T
ENST00000378258.5:c.-149C>T
ENST00000378278.6:c.212C>T
ENST00000378289.8:c.212C>T
ENST00000396817.6:c.-471C>T
ENST00000418843.5:c.-186C>T
ENST00000456122.1:c.-400C>T
NM_001033855.2:c.212C>T
NM_001033857.2:c.-149C>T
NM_001033858.2:c.-471C>T
NM_001289076.1:c.-44+3897C>T
NM_001289077.1:c.-149C>T
NM_001289078.1:c.-78C>T
NM_001289079.1:c.-471C>T
NM_022487.3:c.-78C>T
NR_110297.1:n.719C>T
NM_001350965.1:c.212C>T
NM_001350966.1:c.-78C>T
NM_001350967.1:c.-149C>T
NR_146960.1:n.634C>T
NR_146961.1:n.719C>T
NR_146962.1:n.634C>T
NM_001033857.3:c.-149C>T
NM_001033858.3:c.-471C>T
NM_001289076.2:c.-44+3897C>T
NM_001289077.2:c.-149C>T
NM_001289078.2:c.-78C>T
NM_001289079.2:c.-471C>T
NM_001350965.2:c.212C>T
NM_001350966.2:c.-78C>T
NM_001350967.2:c.-149C>T
NM_022487.4:c.-78C>T
NR_110297.2:n.383C>T
NR_146961.2:n.383C>T
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Uncertain Significance

Not Met criteria codes 4
PM5 PM2 BA1 BS1

Evidence Links 0

Expert Panel

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.212C>T (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Threonine by Methionine at amino acid 71 (p.Thr71Met). The filtering allele frequency (the upper threshold of the 95% CI of 303/1179486 alleles) of the c.212C>T variant in DCLRE1C is 0.0002288 for European (non-Finnish) 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). 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 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.
Not Met criteria codes
PM5
Another missense variant [NM_001033855.3(DCLRE1C):c.211A>C (p.Thr71Pro)] in the same codon has been reported. Despite being classified in ClinVar as Likely Pathogenic, it has not yet been evaluated according to the SCID VCEP specifications. PM5 is not met at this time.
PM2
The filtering allele frequency (the upper threshold of the 95% CI of 303/1179486 alleles) of the c.212C>T variant in DCLRE1C is 0.0002288 for European (non-Finnish) 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
Curation History
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