Variant: NM_001033855.3(DCLRE1C):c.1334G>A (p.Arg445His)

CA5416498

706681 (ClinVar)

Gene: DCLRE1C

Condition: severe combined immunodeficiency due to DCLRE1C deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 1e6799df-33ab-4332-bf70-1d26b54f8444

Approved on: 2024-06-13

Published on: 2024-06-13

HGVS expressions

NM_001033855.3:c.1334G>A
NM_001033855.3(DCLRE1C):c.1334G>A (p.Arg445His)
NC_000010.11:g.14909153C>T
CM000672.2:g.14909153C>T
NC_000010.10:g.14951152C>T
CM000672.1:g.14951152C>T
NC_000010.9:g.14991158C>T
NG_007276.1:g.49943G>A
ENST00000378241.6:c.*1522G>A
ENST00000456122.2:c.*1343-9841G>A
ENST00000489161.2:c.*1057G>A
ENST00000492201.6:c.*328G>A
ENST00000697047.1:c.1334G>A
ENST00000697070.1:c.1334G>A
ENST00000697071.1:c.*1254G>A
ENST00000697072.1:c.*346G>A
ENST00000697073.1:c.*1112G>A
ENST00000697074.1:c.*1112G>A
ENST00000697075.1:c.1334G>A
ENST00000697076.1:c.*346G>A
ENST00000697077.1:c.*1045G>A
ENST00000697078.1:c.*1041G>A
ENST00000697079.1:n.1038G>A
ENST00000697080.1:c.*1198G>A
ENST00000697081.1:c.*1092G>A
ENST00000697082.1:c.*1363G>A
ENST00000697083.1:c.*1139G>A
ENST00000697084.1:c.1391G>A
ENST00000697085.1:c.*1101G>A
ENST00000697086.1:n.3910G>A
ENST00000378278.7:c.1334G>A
ENST00000357717.6:c.989G>A
ENST00000378242.1:c.293G>A
ENST00000378246.6:c.989G>A
ENST00000378249.5:c.989G>A
ENST00000378254.5:c.974G>A
ENST00000378255.5:c.974G>A
ENST00000378258.5:c.974G>A
ENST00000378278.6:c.1334G>A
ENST00000378289.8:c.1157-9841G>A
ENST00000396817.6:c.974G>A
ENST00000492201.5:n.549G>A
NM_001033855.2:c.1334G>A
NM_001033857.2:c.974G>A
NM_001033858.2:c.974G>A
NM_001289076.1:c.989G>A
NM_001289077.1:c.974G>A
NM_001289078.1:c.989G>A
NM_001289079.1:c.974G>A
NM_022487.3:c.989G>A
NR_110297.1:n.2109G>A
NM_001350965.1:c.1334G>A
NM_001350966.1:c.989G>A
NM_001350967.1:c.974G>A
NR_146960.1:n.1701G>A
NR_146961.1:n.1850G>A
NR_146962.1:n.1821G>A
NM_001033857.3:c.974G>A
NM_001033858.3:c.974G>A
NM_001289076.2:c.989G>A
NM_001289077.2:c.974G>A
NM_001289078.2:c.989G>A
NM_001289079.2:c.974G>A
NM_001350965.2:c.1334G>A
NM_001350966.2:c.989G>A
NM_001350967.2:c.974G>A
NM_022487.4:c.989G>A
NR_110297.2:n.1773G>A
NR_146961.2:n.1514G>A

Likely Benign

• Met criteria codes: BS1

• Not Met criteria codes: BS2

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.1334G>A (NM_001033855.3) variant in DCLRE1C is a missense variant predicted to cause substitution of Arginine by Histidine at amino acid 445 (p.Arg445His). The filtering allele frequency (the lower threshold of the 95% CI of 58/44884 alleles) of the c.1334G>A variant in DCLRE1C is 0.001026 for East Asian chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00078) for BS1, and therefore meets this criterion (BS1) To our knowledge, this variant has not been reported in the literature in individuals affected with SCID/DCLRE1C-related conditions or in functional studies. In summary, this variant meets the criteria to be classified as Likely 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: BS1 (VCEP specifications version 1.0).

Met criteria codes

• BS1: The filtering allele frequency (the lower threshold of the 95% CI of 58/44884 alleles) of the c.1334G>A variant in DCLRE1C is 0.001026 for East Asian chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00078) for BS1, and therefore meets this criterion (BS1)

Not Met criteria codes

• BS2: No homozygotes have been observed in gnomAD.