Variant: NM_001033855.3(DCLRE1C):c.1894G>A (p.Glu632Lys)

CA5416379

598004 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: ce865125-3527-4e3a-b583-b842605ccb62

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_001033855.3:c.1894G>A
NM_001033855.3(DCLRE1C):c.1894G>A (p.Glu632Lys)
NC_000010.11:g.14908593C>T
CM000672.2:g.14908593C>T
NC_000010.10:g.14950592C>T
CM000672.1:g.14950592C>T
NC_000010.9:g.14990598C>T
NG_007276.1:g.50503G>A
ENST00000378278.7:c.1894G>A
ENST00000357717.6:c.1549G>A
ENST00000378242.1:c.853G>A
ENST00000378246.6:c.1549G>A
ENST00000378249.5:c.1549G>A
ENST00000378254.5:c.1534G>A
ENST00000378255.5:c.1534G>A
ENST00000378258.5:c.1534G>A
ENST00000378278.6:c.1894G>A
ENST00000378289.8:c.1157-9281G>A
ENST00000396817.6:c.1534G>A
NM_001033855.2:c.1894G>A
NM_001033857.2:c.1534G>A
NM_001033858.2:c.1534G>A
NM_001289076.1:c.1549G>A
NM_001289077.1:c.1534G>A
NM_001289078.1:c.1549G>A
NM_001289079.1:c.1534G>A
NM_022487.3:c.1549G>A
NR_110297.1:n.2669G>A
NM_001350965.1:c.1782+112G>A
NM_001350966.1:c.1437+112G>A
NM_001350967.1:c.1422+112G>A
NR_146960.1:n.2149+112G>A
NR_146961.1:n.2410G>A
NR_146962.1:n.2381G>A
NM_001033857.3:c.1534G>A
NM_001033858.3:c.1534G>A
NM_001289076.2:c.1549G>A
NM_001289077.2:c.1534G>A
NM_001289078.2:c.1549G>A
NM_001289079.2:c.1534G>A
NM_001350965.2:c.1782+112G>A
NM_001350966.2:c.1437+112G>A
NM_001350967.2:c.1422+112G>A
NM_022487.4:c.1549G>A
NR_110297.2:n.2333G>A
NR_146961.2:n.2074G>A

Benign

• Met criteria codes: BA1 BS2_Supporting

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

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The c.1894G>A (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Glutamic Acid by Lysine at amino acid 632 (p.Glu632Lys). The filtering allele frequency (the lower threshold of the 95% CI of 431/91076) of the c.1894G>A variant in DCLRE1C is 0.004306 for South Asian chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00346) for BA1, and therefore meets this criterion (BA1). Additionally, 6 adult homozygous have been reported in the same population (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).

Met criteria codes

• BA1: The filtering allele frequency (the lower threshold of the 95% CI of 431/91076) of the c.1894G>A variant in DCLRE1C is 0.004306 for South Asian 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, 6 adult homozygous have been reported in the same population.