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]
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  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_001033855.3(DCLRE1C):c.572G>A (p.Arg191Gln)

CA5416777

945025 (ClinVar)

Gene: DCLRE1C
Condition: severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: e2adc7ee-f0b4-4e8c-af4c-5c34a05b2a1a
Approved on: 2024-06-13
Published on: 2024-06-13

HGVS expressions

NM_001033855.3:c.572G>A
NM_001033855.3(DCLRE1C):c.572G>A (p.Arg191Gln)
NC_000010.11:g.14934486C>T
CM000672.2:g.14934486C>T
NC_000010.10:g.14976485C>T
CM000672.1:g.14976485C>T
NC_000010.9:g.15016491C>T
NG_007276.1:g.24610G>A
ENST00000378241.6:c.*619G>A
ENST00000456122.2:c.*758G>A
ENST00000489161.2:c.*350G>A
ENST00000492201.6:c.572G>A
ENST00000697047.1:c.572G>A
ENST00000697070.1:c.572G>A
ENST00000697071.1:c.*492G>A
ENST00000697072.1:c.572G>A
ENST00000697073.1:c.*350G>A
ENST00000697074.1:c.*350G>A
ENST00000697075.1:c.572G>A
ENST00000697076.1:c.572G>A
ENST00000697077.1:c.*283G>A
ENST00000697078.1:c.*279G>A
ENST00000697079.1:n.276G>A
ENST00000697080.1:c.*436G>A
ENST00000697081.1:c.*189G>A
ENST00000697082.1:c.*758G>A
ENST00000697083.1:c.*432G>A
ENST00000697084.1:c.572G>A
ENST00000697085.1:c.*339G>A
ENST00000697086.1:n.3009G>A
ENST00000697087.1:c.*492G>A
ENST00000697088.1:c.*189G>A
ENST00000697089.1:c.*492G>A
ENST00000697090.1:n.580G>A
ENST00000378278.7:c.572G>A
ENST00000357717.6:c.227G>A
ENST00000378241.5:c.212G>A
ENST00000378246.6:c.227G>A
ENST00000378249.5:c.227G>A
ENST00000378254.5:c.212G>A
ENST00000378255.5:c.212G>A
ENST00000378258.5:c.212G>A
ENST00000378278.6:c.572G>A
ENST00000378289.8:c.572G>A
ENST00000396817.6:c.212G>A
ENST00000418843.5:c.134G>A
NM_001033855.2:c.572G>A
NM_001033857.2:c.212G>A
NM_001033858.2:c.212G>A
NM_001289076.1:c.227G>A
NM_001289077.1:c.212G>A
NM_001289078.1:c.227G>A
NM_001289079.1:c.212G>A
NM_022487.3:c.227G>A
NR_110297.1:n.1206G>A
NM_001350965.1:c.572G>A
NM_001350966.1:c.227G>A
NM_001350967.1:c.212G>A
NR_146960.1:n.994G>A
NR_146961.1:n.1023G>A
NR_146962.1:n.994G>A
NM_001033857.3:c.212G>A
NM_001033858.3:c.212G>A
NM_001289076.2:c.227G>A
NM_001289077.2:c.212G>A
NM_001289078.2:c.227G>A
NM_001289079.2:c.212G>A
NM_001350965.2:c.572G>A
NM_001350966.2:c.227G>A
NM_001350967.2:c.212G>A
NM_022487.4:c.227G>A
NR_110297.2:n.870G>A
NR_146961.2:n.687G>A

Likely Benign

Met criteria codes 2
BS2_Supporting BS1
Not Met criteria codes 1
PM2

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.572G>A (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Arginine by Glutamine at amino acid 191 (p.Arg191Gln). The filtering allele frequency (the upper threshold of the 95% CI of 4/91084 alleles) of the c.572G>A variant in DCLRE1C is 0.00001425 for South Asian chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting. However, 2 homozygous individuals have been reported in the Middle Eastern population: 18/6062 alleles, freq: 0.002969. Therefore, PM2 is not applicable, and BS2 is met at the Supporting level (BS2_Supporting). The Middle Eastern population: 18/6062 alleles, freq: 0.002969, meet the BS1 threshold (>0.00078), so BS1 is met. 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 Likely 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: BS2_Supporting and BS1 (VCEP specifications version 1).
Met criteria codes
BS2_Supporting
gnomAD v4 presents two homozygous occurrences in the Middle Eastern population. BS2_Supporting.
BS1
The Middle Eastern population: 18/6062 alleles, freq: 0.002969 meet with BS1 threshold (>0.00078).
Not Met criteria codes
PM2
The filtering allele frequency (the upper threshold of the 95% CI of 4/91084 alleles) of the c.572G>A variant in DCLRE1C is 0.00001425 for South Asian chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting. However, 2 homozygous individuals have been reported in the Middle Eastern population: 18/6062 alleles, freq: 0.002969. Therefore, PM2 is not applicable.
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