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.728A>G (p.His243Arg)

CA5416704

257180 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 7e71d964-bb7a-40e1-9385-3393a4499ac5

HGVS expressions

NM_001033855.3:c.728A>G

NM_001033855.3(DCLRE1C):c.728A>G (p.His243Arg)

NC_000010.11:g.14932906T>C

CM000672.2:g.14932906T>C

NC_000010.10:g.14974905T>C

CM000672.1:g.14974905T>C

NC_000010.9:g.15014911T>C

NG_007276.1:g.26190A>G

ENST00000378278.7:c.728A>G

ENST00000357717.6:c.383A>G

ENST00000378246.6:c.383A>G

ENST00000378249.5:c.383A>G

ENST00000378254.5:c.368A>G

ENST00000378255.5:c.368A>G

ENST00000378258.5:c.368A>G

ENST00000378278.6:c.728A>G

ENST00000378289.8:c.728A>G

ENST00000396817.6:c.368A>G

ENST00000418843.5:c.290A>G

NM_001033855.2:c.728A>G

NM_001033857.2:c.368A>G

NM_001033858.2:c.368A>G

NM_001289076.1:c.383A>G

NM_001289077.1:c.368A>G

NM_001289078.1:c.383A>G

NM_001289079.1:c.368A>G

NM_022487.3:c.383A>G

NR_110297.1:n.1362A>G

NM_001350965.1:c.728A>G

NM_001350966.1:c.383A>G

NM_001350967.1:c.368A>G

NR_146960.1:n.1150A>G

NR_146961.1:n.1179A>G

NR_146962.1:n.1150A>G

NM_001033857.3:c.368A>G

NM_001033858.3:c.368A>G

NM_001289076.2:c.383A>G

NM_001289077.2:c.368A>G

NM_001289078.2:c.383A>G

NM_001289079.2:c.368A>G

NM_001350965.2:c.728A>G

NM_001350966.2:c.383A>G

NM_001350967.2:c.368A>G

NM_022487.4:c.383A>G

NR_110297.2:n.1026A>G

NR_146961.2:n.843A>G

Benign

BA1 BS2_Supporting

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 c.728A>G (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Histidine by Arginine at amino acid 243 (p.His243Arg). The filtering allele frequency (the lower threshold of the 95% CI of 13221/60002) of the c.728A>G variant in DCLRE1C is 0.2249 for Admixed American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Additionally, 23214 adult homozygous have been reported (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to DCLRE1C deficiency, based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BA1 and BS2_Supporting (VCEP specifications version 1).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 13221/60002) of the c.728A>G variant in DCLRE1C is 0.2249 for Admixed American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1).

BS2_Supporting

Additionally, 23214 adult homozygous have been reported (BS2_Supporting).

Approved on: 2024-01-23

Published on: 2024-01-23

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