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]

Variant: NM_001033855.3(DCLRE1C):c.169G>T (p.Val57Phe)

CA5416981

299322 (ClinVar)

Gene: DCLRE1C
Condition: severe combined immunodeficiency due to DCLRE1C deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 5d86fba3-929a-4de6-b38f-280dcf653312
Approved on: 2024-01-17
Published on: 2024-01-17

HGVS expressions

NM_001033855.3:c.169G>T
NM_001033855.3(DCLRE1C):c.169G>T (p.Val57Phe)
NC_000010.11:g.14945182C>A
CM000672.2:g.14945182C>A
NC_000010.10:g.14987181C>A
CM000672.1:g.14987181C>A
NC_000010.9:g.15027187C>A
NG_007276.1:g.13914G>T
ENST00000378278.7:c.169G>T
ENST00000357717.6:c.-44+3854G>T
ENST00000378241.5:c.-319G>T
ENST00000378246.6:c.-121G>T
ENST00000378249.5:c.-121G>T
ENST00000378254.5:c.-192G>T
ENST00000378255.5:c.-514G>T
ENST00000378258.5:c.-192G>T
ENST00000378278.6:c.169G>T
ENST00000378289.8:c.169G>T
ENST00000396817.6:c.-514G>T
ENST00000418843.5:c.-229G>T
ENST00000456122.1:c.-443G>T
NM_001033855.2:c.169G>T
NM_001033857.2:c.-192G>T
NM_001033858.2:c.-514G>T
NM_001289076.1:c.-44+3854G>T
NM_001289077.1:c.-192G>T
NM_001289078.1:c.-121G>T
NM_001289079.1:c.-514G>T
NM_022487.3:c.-121G>T
NR_110297.1:n.676G>T
NM_001350965.1:c.169G>T
NM_001350966.1:c.-121G>T
NM_001350967.1:c.-192G>T
NR_146960.1:n.591G>T
NR_146961.1:n.676G>T
NR_146962.1:n.591G>T
NM_001033857.3:c.-192G>T
NM_001033858.3:c.-514G>T
NM_001289076.2:c.-44+3854G>T
NM_001289077.2:c.-192G>T
NM_001289078.2:c.-121G>T
NM_001289079.2:c.-514G>T
NM_001350965.2:c.169G>T
NM_001350966.2:c.-121G>T
NM_001350967.2:c.-192G>T
NM_022487.4:c.-121G>T
NR_110297.2:n.340G>T
NR_146961.2:n.340G>T
More

Likely Benign

Met criteria codes 1
BS1
Not Met criteria codes 3
PM2 BA1 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.169G>T (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause a substitution of Valine by Phenylalanine at amino acid 57 (p.Val57Phe). The popmax filtering allele frequency in gnomAD v2.1. is 0.0001675 (based on 29/128916 alleles in the non-Finnish European population), which is below the SCID VCEP established threshold of >0.00078. However, the highest MAF is in the Ashkenazi Jewish population at 0.005896 (61/10346 alleles and NO homozygotes reported), which is above the SCID VCEP established threshold of >00078. As this population is not known to have a higher disease prevalence, this is considered to meet BS1. After a comprehensive literature search, the variant has not been found in individuals with SCID due to DCLRE1C deficiency. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive SCID based on the ACMG criteria applied: BS1, as specified by the ClinGen SCID VCEP (VCEP specifications version 1).
Met criteria codes
BS1
The popmax filtering allele frequency in gnomAD v2.1. is 0.0001675 (based on 29/128916 alleles in the non-Finnish European population), which is below the SCID VCEP established threshold of >0.00078. However, the highest MAF is in the Ashkenazi Jewish population at 0.005896 (61/10346 alleles and NO homozygotes reported), which is above the SCID VCEP established threshold of >00078. As this population is not known to have a higher disease prevalence, this is considered to meet BS1.
Not Met criteria codes
PM2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BA1
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
Curation History
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