Variant: NM_001033855.3(DCLRE1C):c.475A>T (p.Ile159Phe)

CA5416824

1511542 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 2871c1c4-cab1-4fb9-b75e-7b8763c159c0

Approved on: 2024-06-13

Published on: 2024-06-13

HGVS expressions

NM_001033855.3:c.475A>T
NM_001033855.3(DCLRE1C):c.475A>T (p.Ile159Phe)
NC_000010.11:g.14934765T>A
CM000672.2:g.14934765T>A
NC_000010.10:g.14976764T>A
CM000672.1:g.14976764T>A
NC_000010.9:g.15016770T>A
NG_007276.1:g.24331A>T
ENST00000378241.6:c.*522A>T
ENST00000456122.2:c.*661A>T
ENST00000489161.2:c.*253A>T
ENST00000492201.6:c.475A>T
ENST00000697047.1:c.475A>T
ENST00000697070.1:c.475A>T
ENST00000697071.1:c.*395A>T
ENST00000697072.1:c.475A>T
ENST00000697073.1:c.*253A>T
ENST00000697074.1:c.*253A>T
ENST00000697075.1:c.475A>T
ENST00000697076.1:c.475A>T
ENST00000697077.1:c.*186A>T
ENST00000697078.1:c.*182A>T
ENST00000697079.1:n.179A>T
ENST00000697080.1:c.*339A>T
ENST00000697081.1:c.*92A>T
ENST00000697082.1:c.*661A>T
ENST00000697083.1:c.*335A>T
ENST00000697084.1:c.475A>T
ENST00000697085.1:c.*242A>T
ENST00000697086.1:n.2912A>T
ENST00000697087.1:c.*395A>T
ENST00000697088.1:c.*92A>T
ENST00000697089.1:c.*395A>T
ENST00000697090.1:n.483A>T
ENST00000378278.7:c.475A>T
ENST00000357717.6:c.130A>T
ENST00000378241.5:c.115A>T
ENST00000378246.6:c.130A>T
ENST00000378249.5:c.130A>T
ENST00000378254.5:c.115A>T
ENST00000378255.5:c.115A>T
ENST00000378258.5:c.115A>T
ENST00000378278.6:c.475A>T
ENST00000378289.8:c.475A>T
ENST00000396817.6:c.115A>T
ENST00000418843.5:c.37A>T
ENST00000456122.1:c.130A>T
NM_001033855.2:c.475A>T
NM_001033857.2:c.115A>T
NM_001033858.2:c.115A>T
NM_001289076.1:c.130A>T
NM_001289077.1:c.115A>T
NM_001289078.1:c.130A>T
NM_001289079.1:c.115A>T
NM_022487.3:c.130A>T
NR_110297.1:n.1109A>T
NM_001350965.1:c.475A>T
NM_001350966.1:c.130A>T
NM_001350967.1:c.115A>T
NR_146960.1:n.897A>T
NR_146961.1:n.926A>T
NR_146962.1:n.897A>T
NM_001033857.3:c.115A>T
NM_001033858.3:c.115A>T
NM_001289076.2:c.130A>T
NM_001289077.2:c.115A>T
NM_001289078.2:c.130A>T
NM_001289079.2:c.115A>T
NM_001350965.2:c.475A>T
NM_001350966.2:c.130A>T
NM_001350967.2:c.115A>T
NM_022487.4:c.130A>T
NR_110297.2:n.773A>T
NR_146961.2:n.590A>T

Uncertain Significance

• Met criteria codes: PM2_Supporting

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

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The c.475A>T (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Isoleucine by Phenylalanine at amino acid 159 (p.Ile159Phe). The filtering allele frequency (the upper threshold of the 95% CI of 34/1179098 alleles) of the c.475A>T variant in DCLRE1C is 0.00002075 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). 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: PM2_Supporting (VCEP specifications version 1).

Met criteria codes

• PM2_Supporting: The filtering allele frequency (the upper threshold of the 95% CI of 34/1179098 alleles) of the c.475A>T variant in DCLRE1C is 0.00002075 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD.