Variant: NM_000022.4(ADA):c.757C>T (p.Arg253Trp)

CA9871538

618516 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 5dfdb530-7ee4-4697-a438-5f25766631d2

Approved on: 2024-01-10

Published on: 2024-01-10

HGVS expressions

NM_000022.4:c.757C>T
NM_000022.4(ADA):c.757C>T (p.Arg253Trp)
NC_000020.11:g.44622852G>A
CM000682.2:g.44622852G>A
NC_000020.10:g.43251493G>A
CM000682.1:g.43251493G>A
NC_000020.9:g.42684907G>A
NG_007385.1:g.33884C>T
ENST00000372874.9:c.757C>T
ENST00000372874.8:c.757C>T
ENST00000372887.5:c.152-1081G>A
ENST00000464097.5:n.507C>T
ENST00000492931.5:n.917C>T
ENST00000536532.5:c.757C>T
ENST00000537820.1:c.685C>T
ENST00000539235.5:c.*141C>T
NM_000022.2:c.757C>T
NM_000022.3:c.757C>T
NM_001322050.1:c.352C>T
NM_001322051.1:c.685C>T
NR_136160.1:n.908C>T
NM_001322050.2:c.352C>T
NM_001322051.2:c.685C>T
NR_136160.2:n.849C>T

Uncertain Significance

• Not Met criteria codes: PM2

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 ADA Version 1.0.0

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000022.4(ADA):c.757C>T is a missense variant predicted to cause substitution of Arginine by Tryptophan at amino acid 253 (p.Arg253Trp).The filtering allele frequency (the upper threshold of the 95% CI of 101/1180020) of the c.757C>T variant in ADA is 0.00007452 for European Non-Finnish chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting.However, 1 homozygote was reported (PM2 not met). There are no publications for this variant in the literature. Another missense variant R253P in the same codon has been reported (PMIDs : 8258146,9758612) (not classified by SCID VCEP yet):PM5 not evaluated. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to ADA deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: No criteria met (VCEP specifications version 1).

Not Met criteria codes

• PM2: The filtering allele frequency (the upper threshold of the 95% CI of 101/1180020) of the c.757C>T variant in ADA is 0.00007452 for European Non-Finnish chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting.However, 1 homozygote was reported (PM2 not met).