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Variant: NM_001033855.3(DCLRE1C):c.623C>T (p.Ala208Val)

CA376059471

1515797 (ClinVar)

Gene: DCLRE1C
Condition: severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 6a2c908f-332e-494a-a5ad-74da2141a498
Approved on: 2024-02-15
Published on: 2024-02-15

HGVS expressions

NM_001033855.3:c.623C>T
NM_001033855.3(DCLRE1C):c.623C>T (p.Ala208Val)
NC_000010.11:g.14934435G>A
CM000672.2:g.14934435G>A
NC_000010.10:g.14976434G>A
CM000672.1:g.14976434G>A
NC_000010.9:g.15016440G>A
NG_007276.1:g.24661C>T
ENST00000378241.6:c.*670C>T
ENST00000456122.2:c.*809C>T
ENST00000489161.2:c.*401C>T
ENST00000492201.6:c.623C>T
ENST00000697047.1:c.623C>T
ENST00000697070.1:c.623C>T
ENST00000697071.1:c.*543C>T
ENST00000697072.1:c.623C>T
ENST00000697073.1:c.*401C>T
ENST00000697074.1:c.*401C>T
ENST00000697075.1:c.623C>T
ENST00000697076.1:c.623C>T
ENST00000697077.1:c.*334C>T
ENST00000697078.1:c.*330C>T
ENST00000697079.1:n.327C>T
ENST00000697080.1:c.*487C>T
ENST00000697081.1:c.*240C>T
ENST00000697082.1:c.*809C>T
ENST00000697083.1:c.*483C>T
ENST00000697084.1:c.623C>T
ENST00000697085.1:c.*390C>T
ENST00000697086.1:n.3060C>T
ENST00000697087.1:c.*543C>T
ENST00000697088.1:c.*240C>T
ENST00000697089.1:c.*543C>T
ENST00000697090.1:n.631C>T
ENST00000378278.7:c.623C>T
ENST00000357717.6:c.278C>T
ENST00000378246.6:c.278C>T
ENST00000378249.5:c.278C>T
ENST00000378254.5:c.263C>T
ENST00000378255.5:c.263C>T
ENST00000378258.5:c.263C>T
ENST00000378278.6:c.623C>T
ENST00000378289.8:c.623C>T
ENST00000396817.6:c.263C>T
ENST00000418843.5:c.185C>T
NM_001033855.2:c.623C>T
NM_001033857.2:c.263C>T
NM_001033858.2:c.263C>T
NM_001289076.1:c.278C>T
NM_001289077.1:c.263C>T
NM_001289078.1:c.278C>T
NM_001289079.1:c.263C>T
NM_022487.3:c.278C>T
NR_110297.1:n.1257C>T
NM_001350965.1:c.623C>T
NM_001350966.1:c.278C>T
NM_001350967.1:c.263C>T
NR_146960.1:n.1045C>T
NR_146961.1:n.1074C>T
NR_146962.1:n.1045C>T
NM_001033857.3:c.263C>T
NM_001033858.3:c.263C>T
NM_001289076.2:c.278C>T
NM_001289077.2:c.263C>T
NM_001289078.2:c.278C>T
NM_001289079.2:c.263C>T
NM_001350965.2:c.623C>T
NM_001350966.2:c.278C>T
NM_001350967.2:c.263C>T
NM_022487.4:c.278C>T
NR_110297.2:n.921C>T
NR_146961.2:n.738C>T

Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 1
PM1

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.623C>T (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Alanine by Valine at amino acid 208 (p.Ala208Val). The filtering allele frequency (the upper threshold of the 95% CI of 11/1180008 alleles) of the c.623C>T variant in DCLRE1C is 0.000005310 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 11/1180008 alleles) of the c.623C>T variant in DCLRE1C is 0.000005310 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.
Not Met criteria codes
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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