Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_001033855.3(DCLRE1C):c.959C>G (p.Ser320Cys)

CA290573

137073 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1e415979-5d92-452e-a666-3a4ecd34b44e

HGVS expressions

NM_001033855.3:c.959C>G

NM_001033855.3(DCLRE1C):c.959C>G (p.Ser320Cys)

NC_000010.11:g.14926856G>C

CM000672.2:g.14926856G>C

NC_000010.10:g.14968855G>C

CM000672.1:g.14968855G>C

NC_000010.9:g.15008861G>C

NG_007276.1:g.32240C>G

ENST00000378278.7:c.959C>G

ENST00000357717.6:c.614C>G

ENST00000378246.6:c.614C>G

ENST00000378249.5:c.614C>G

ENST00000378254.5:c.599C>G

ENST00000378255.5:c.599C>G

ENST00000378258.5:c.599C>G

ENST00000378278.6:c.959C>G

ENST00000378289.8:c.959C>G

ENST00000396817.6:c.599C>G

ENST00000489161.1:n.47+1160C>G

ENST00000492201.5:n.109C>G

NM_001033855.2:c.959C>G

NM_001033857.2:c.599C>G

NM_001033858.2:c.599C>G

NM_001289076.1:c.614C>G

NM_001289077.1:c.599C>G

NM_001289078.1:c.614C>G

NM_001289079.1:c.599C>G

NM_022487.3:c.614C>G

NR_110297.1:n.1593C>G

NM_001350965.1:c.959C>G

NM_001350966.1:c.614C>G

NM_001350967.1:c.599C>G

NR_146960.1:n.1339+1160C>G

NR_146961.1:n.1410C>G

NR_146962.1:n.1381C>G

NM_001033857.3:c.599C>G

NM_001033858.3:c.599C>G

NM_001289076.2:c.614C>G

NM_001289077.2:c.599C>G

NM_001289078.2:c.614C>G

NM_001289079.2:c.599C>G

NM_001350965.2:c.959C>G

NM_001350966.2:c.614C>G

NM_001350967.2:c.599C>G

NM_022487.4:c.614C>G

NR_110297.2:n.1257C>G

NR_146961.2:n.1074C>G

Benign

BS2_Supporting BA1

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

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 NM_001033855.3:c.959C>G variant in DCLRE1C is a missense variant predicted to cause substitution of serine by cysteine at amino acid 320 (p.Ser320Cys). This variant has an allele frequency of 0.03553 in the African / African American population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for DCLRE1C (>0.00346). In addition, 16 adult homozygous individuals with this variant are present in gnomAD v2.1.1 (in African/African American population)(BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting as specified by the ClinGen SCID VCEP (VCEP specifications version 1).

BS2_Supporting

16 adult homozygous individuals with this variant are present in gnomADv2.1.1 (in African/African American population)(BS2_Supporting).

BA1

The highest minor allele frequency in gnomAD is 0.03553 (887/24962) in the African/African-American population in gnomAD. This is higher than the cutoff for BA1 set by ClinGen VCEP for DCLRE1C (>0.00346). Therefore BA1 is met. This variant also has 16 homozygotes in gnomAD.

Approved on: 2024-01-17

Published on: 2024-01-17

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