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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Variant: NM_001033855.3(DCLRE1C):c.614A>T (p.Asn205Ile)

CA203395661

1057857 (ClinVar)

Gene: DCLRE1C
Condition: severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 55384e5c-b292-4c8c-adb2-645ff30d7b6f
Approved on: 2024-02-15
Published on: 2024-02-15

HGVS expressions

NM_001033855.3:c.614A>T
NM_001033855.3(DCLRE1C):c.614A>T (p.Asn205Ile)
NC_000010.11:g.14934444T>A
CM000672.2:g.14934444T>A
NC_000010.10:g.14976443T>A
CM000672.1:g.14976443T>A
NC_000010.9:g.15016449T>A
NG_007276.1:g.24652A>T
ENST00000378241.6:c.*661A>T
ENST00000456122.2:c.*800A>T
ENST00000489161.2:c.*392A>T
ENST00000492201.6:c.614A>T
ENST00000697047.1:c.614A>T
ENST00000697070.1:c.614A>T
ENST00000697071.1:c.*534A>T
ENST00000697072.1:c.614A>T
ENST00000697073.1:c.*392A>T
ENST00000697074.1:c.*392A>T
ENST00000697075.1:c.614A>T
ENST00000697076.1:c.614A>T
ENST00000697077.1:c.*325A>T
ENST00000697078.1:c.*321A>T
ENST00000697079.1:n.318A>T
ENST00000697080.1:c.*478A>T
ENST00000697081.1:c.*231A>T
ENST00000697082.1:c.*800A>T
ENST00000697083.1:c.*474A>T
ENST00000697084.1:c.614A>T
ENST00000697085.1:c.*381A>T
ENST00000697086.1:n.3051A>T
ENST00000697087.1:c.*534A>T
ENST00000697088.1:c.*231A>T
ENST00000697089.1:c.*534A>T
ENST00000697090.1:n.622A>T
ENST00000378278.7:c.614A>T
ENST00000357717.6:c.269A>T
ENST00000378246.6:c.269A>T
ENST00000378249.5:c.269A>T
ENST00000378254.5:c.254A>T
ENST00000378255.5:c.254A>T
ENST00000378258.5:c.254A>T
ENST00000378278.6:c.614A>T
ENST00000378289.8:c.614A>T
ENST00000396817.6:c.254A>T
ENST00000418843.5:c.176A>T
NM_001033855.2:c.614A>T
NM_001033857.2:c.254A>T
NM_001033858.2:c.254A>T
NM_001289076.1:c.269A>T
NM_001289077.1:c.254A>T
NM_001289078.1:c.269A>T
NM_001289079.1:c.254A>T
NM_022487.3:c.269A>T
NR_110297.1:n.1248A>T
NM_001350965.1:c.614A>T
NM_001350966.1:c.269A>T
NM_001350967.1:c.254A>T
NR_146960.1:n.1036A>T
NR_146961.1:n.1065A>T
NR_146962.1:n.1036A>T
NM_001033857.3:c.254A>T
NM_001033858.3:c.254A>T
NM_001289076.2:c.269A>T
NM_001289077.2:c.254A>T
NM_001289078.2:c.269A>T
NM_001289079.2:c.254A>T
NM_001350965.2:c.614A>T
NM_001350966.2:c.269A>T
NM_001350967.2:c.254A>T
NM_022487.4:c.269A>T
NR_110297.2:n.912A>T
NR_146961.2:n.729A>T

Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 3
PS1 PM5 BS2

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.614A>T (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Asparagine by Isoleucine at amino acid 205 (p.Asn205Ile). The filtering allele frequency (the upper threshold of the 95% CI of 13/1180046 alleles) of the c.614A>T variant in DCLRE1C is 0.000005750 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 13/1180046 alleles) of the c.614A>T variant in DCLRE1C is 0.000005750 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
PS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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