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

Variant: NM_001033855.3(DCLRE1C):c.973-1801T>A

CA203388902

1679474 (ClinVar)

Gene: DCLRE1C (HGNC:64421)
Condition: severe combined immunodeficiency due to DCLRE1C deficiency (MONDO:0011225)
Inheritance Mode: Autosomal recessive inheritance
UUID: c5f15080-5d5f-4040-9c29-844b3b06be47
Approved on: 2024-01-17
Published on: 2024-01-17

HGVS expressions

NM_001033855.3:c.973-1801T>A
NM_001033855.3(DCLRE1C):c.973-1801T>A
NC_000010.11:g.14924870A>T
CM000672.2:g.14924870A>T
NC_000010.10:g.14966869A>T
CM000672.1:g.14966869A>T
NC_000010.9:g.15006875A>T
NG_007276.1:g.34226T>A
ENST00000378241.6:c.*1020-1801T>A
ENST00000456122.2:c.*1159-1801T>A
ENST00000489161.2:c.*696-1801T>A
ENST00000492201.6:c.973-1801T>A
ENST00000697047.1:c.973-1801T>A
ENST00000697070.1:c.973-1801T>A
ENST00000697071.1:c.*893-1801T>A
ENST00000697072.1:c.918-1801T>A
ENST00000697073.1:c.*751-1801T>A
ENST00000697074.1:c.*751-1801T>A
ENST00000697075.1:c.973-1801T>A
ENST00000697076.1:c.918-1801T>A
ENST00000697077.1:c.*684-1801T>A
ENST00000697078.1:c.*680-1801T>A
ENST00000697079.1:n.677-1801T>A
ENST00000697080.1:c.*837-1801T>A
ENST00000697081.1:c.*590-1801T>A
ENST00000697082.1:c.*1002-1801T>A
ENST00000697083.1:c.*778-1801T>A
ENST00000697084.1:c.1029+276T>A
ENST00000697085.1:c.*740-1801T>A
ENST00000697086.1:n.3410-1801T>A
ENST00000697087.1:c.*893-1801T>A
ENST00000697088.1:c.*590-1801T>A
ENST00000697089.1:c.*893-1801T>A
ENST00000378278.7:c.973-1801T>A
ENST00000357717.6:c.628-1801T>A
ENST00000378246.6:c.628-1801T>A
ENST00000378249.5:c.628-1801T>A
ENST00000378254.5:c.613-1801T>A
ENST00000378255.5:c.613-1801T>A
ENST00000378258.5:c.613-1801T>A
ENST00000378278.6:c.973-1801T>A
ENST00000378289.8:c.973-1801T>A
ENST00000396817.6:c.613-1801T>A
ENST00000489161.1:n.48-1801T>A
ENST00000492201.5:n.123-1801T>A
NM_001033855.2:c.973-1801T>A
NM_001033857.2:c.613-1801T>A
NM_001033858.2:c.613-1801T>A
NM_001289076.1:c.628-1801T>A
NM_001289077.1:c.613-1801T>A
NM_001289078.1:c.628-1801T>A
NM_001289079.1:c.613-1801T>A
NM_022487.3:c.628-1801T>A
NR_110297.1:n.1607-1801T>A
NM_001350965.1:c.973-1801T>A
NM_001350966.1:c.628-1801T>A
NM_001350967.1:c.613-1801T>A
NR_146960.1:n.1340-1801T>A
NR_146961.1:n.1424-1801T>A
NR_146962.1:n.1395-1801T>A
NM_001033857.3:c.613-1801T>A
NM_001033858.3:c.613-1801T>A
NM_001289076.2:c.628-1801T>A
NM_001289077.2:c.613-1801T>A
NM_001289078.2:c.628-1801T>A
NM_001289079.2:c.613-1801T>A
NM_001350965.2:c.973-1801T>A
NM_001350966.2:c.628-1801T>A
NM_001350967.2:c.613-1801T>A
NM_022487.4:c.628-1801T>A
NR_110297.2:n.1271-1801T>A
NR_146961.2:n.1088-1801T>A
More

Uncertain Significance

Met criteria codes 1
BP7
Not Met criteria codes 3
BS1 PM2 BA1

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.973-1801T>A (NM_001033855.3) variant in DCLRE1C is an intronic variant which locates in the deep intronic region in the intron 11. It is not predicted to impact splicing by SpliceAI, varSEAK, and NNSplice. BP7 is met. The highest population minor allele frequency in gnomAD v2.1.1 is 0.0004608 (4/8180 alleles) in African/African American population, which is lower than the SCID-VCEP threshold for BS1 (>0.00078) and BA1 (>0.00346) but higher than the threshold (<0.00003266) for PM2_Supporting (BS1 not met, BA1 not met, PM2_Supporting not met). To our knowledge, this variant has not been reported in the literature in individuals affected with DCLRE1C/SCID conditions or in functional studies. Due to insufficient evidence, this variant is classified as a variant of uncertain significance for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0).
Met criteria codes
BP7
The c.973-1801T>A (NM_001033855.3) variant in DCLRE1C is an intronic variant which locates in the deep intronic region in the intron 11. It is not predicted to impact splicing by SpliceAI, varSEAK, and NNSplice. BP7 is met.
Not Met criteria codes
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM2
The highest population minor allele frequency in gnomAD v2.1.1 is 0.0004608 (4/8180 alleles) in African/African American population, which is lower than the SCID-VCEP threshold for BS1 (>0.00078) and BA1 (>0.00346) but higher than the threshold (<0.00003266) for PM2_Supporting (BS1 not met, BA1 not met, PM2_Supporting not met).
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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