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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001033855.3(DCLRE1C):c.25G>A (p.Ala9Thr)

CA376066110

958156 (ClinVar)

Gene: DCLRE1C
Condition: severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: f6696015-fb44-4ba5-a42e-a99d939bd088
Approved on: 2024-04-01
Published on: 2024-04-01

HGVS expressions

NM_001033855.3:c.25G>A
NM_001033855.3(DCLRE1C):c.25G>A (p.Ala9Thr)
NC_000010.11:g.14953986C>T
CM000672.2:g.14953986C>T
NC_000010.10:g.14995985C>T
CM000672.1:g.14995985C>T
NC_000010.9:g.15035991C>T
NG_007276.1:g.5110G>A
ENST00000378241.6:c.25G>A
ENST00000456122.2:c.25G>A
ENST00000489161.2:c.25G>A
ENST00000492201.6:c.25G>A
ENST00000697047.1:c.25G>A
ENST00000697070.1:c.25G>A
ENST00000697071.1:c.25G>A
ENST00000697072.1:c.25G>A
ENST00000697073.1:c.25G>A
ENST00000697074.1:c.25G>A
ENST00000697075.1:c.25G>A
ENST00000697076.1:c.25G>A
ENST00000697077.1:c.25G>A
ENST00000697078.1:c.25G>A
ENST00000697080.1:c.25G>A
ENST00000697081.1:c.25G>A
ENST00000697082.1:c.25G>A
ENST00000697083.1:c.25G>A
ENST00000697084.1:c.25G>A
ENST00000697085.1:c.25G>A
ENST00000697087.1:c.25G>A
ENST00000697088.1:c.25G>A
ENST00000697089.1:c.25G>A
ENST00000697091.1:n.86G>A
ENST00000378278.7:c.25G>A
ENST00000357717.6:c.-180G>A
ENST00000378241.5:c.-548G>A
ENST00000378246.6:c.-265G>A
ENST00000378249.5:c.-213G>A
ENST00000378254.5:c.-467G>A
ENST00000378255.5:c.-789G>A
ENST00000378258.5:c.-421G>A
ENST00000378278.6:c.25G>A
ENST00000378289.8:c.25G>A
ENST00000396817.6:c.-743G>A
ENST00000418843.5:c.-504G>A
ENST00000456122.1:c.-672G>A
NM_001033855.2:c.25G>A
NM_001033857.2:c.-421G>A
NM_001033858.2:c.-743G>A
NM_001289076.1:c.-180G>A
NM_001289077.1:c.-467G>A
NM_001289078.1:c.-213G>A
NM_001289079.1:c.-789G>A
NM_022487.3:c.-265G>A
NR_110297.1:n.447G>A
NM_001350965.1:c.25G>A
NM_001350966.1:c.-213G>A
NM_001350967.1:c.-421G>A
NR_146960.1:n.447G>A
NR_146961.1:n.447G>A
NR_146962.1:n.447G>A
NM_001033857.3:c.-421G>A
NM_001033858.3:c.-743G>A
NM_001289076.2:c.-180G>A
NM_001289077.2:c.-467G>A
NM_001289078.2:c.-213G>A
NM_001289079.2:c.-789G>A
NM_001350965.2:c.25G>A
NM_001350966.2:c.-213G>A
NM_001350967.2:c.-421G>A
NM_022487.4:c.-265G>A
NR_110297.2:n.111G>A
NR_146961.2:n.111G>A
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Uncertain Significance

Met criteria codes 1
PM2_Supporting

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.25G>A (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause the substitution of Alanine by Threonine at amino acid 9 (p.Ala9Thr). The highest population minor allele frequency in gnomAD v4 is 0.00003022 (1/33086 alleles) in the "Remaining" population, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting. Despite the "Remaining" being considered a bottleneck population in gnomad v4, as no other alleles have been described in all other populations, PM2_Supporting still can be applied (PM2_Supporting). Allele frequency considering all exomes is 0.000001591, 1/628590 alleles. 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 is classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency, based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): PM2_Supporting.
Met criteria codes
PM2_Supporting
The highest population minor allele frequency in gnomAD v4 is 0.00003022 (1/33086 alleles) in the "Remaining" population, which is lower than the ClinGen SCID VCEP threshold (<0.00003266) for PM2_Supporting. Despite the "Remaining" being considered as a bottleneck population in gnomad v4, as no other alleles have been described in all other populations, PM2_Supporting still can be applied (PM2_Supporting). Allele frequency considering all exomes is 0.000001591, 1/628590 alleles.
Curation History
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