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]

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Variant: NM_000022.4(ADA):c.899T>G (p.Phe300Cys)

CA9871470

897016 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3d04b3e3-b3c9-4a74-990c-d85b6725a0fa

Approved on: 2024-04-23

Published on: 2024-04-23

HGVS expressions

NM_000022.4:c.899T>G

NM_000022.4(ADA):c.899T>G (p.Phe300Cys)

NC_000020.11:g.44621094A>C

CM000682.2:g.44621094A>C

NC_000020.10:g.43249735A>C

CM000682.1:g.43249735A>C

NC_000020.9:g.42683149A>C

NG_007385.1:g.35642T>G

ENST00000492931.6:n.1066T>G

ENST00000536076.2:c.746T>G

ENST00000536532.6:c.*42T>G

ENST00000537820.2:c.827T>G

ENST00000539235.6:c.*283T>G

ENST00000695889.1:c.374T>G

ENST00000695890.1:n.4394T>G

ENST00000695891.1:c.439T>G

ENST00000695927.1:c.977T>G

ENST00000695949.1:c.824T>G

ENST00000695956.1:c.54T>G

ENST00000695957.1:c.*390T>G

ENST00000695991.1:c.437T>G

ENST00000695992.1:c.*42T>G

ENST00000695993.1:c.899T>G

ENST00000695994.1:c.*42T>G

ENST00000695995.1:c.509T>G

ENST00000695996.1:n.981T>G

ENST00000696003.1:n.2683T>G

ENST00000696004.1:n.1067T>G

ENST00000696005.1:c.349T>G

ENST00000696006.1:c.*42T>G

ENST00000696007.1:c.826T>G

ENST00000696008.1:n.3253T>G

ENST00000696017.1:c.896T>G

ENST00000696034.1:c.*42T>G

ENST00000696035.1:n.1085T>G

ENST00000696036.1:n.1600T>G

ENST00000696037.1:n.2576T>G

ENST00000696038.1:c.*656T>G

ENST00000696039.1:n.1263T>G

ENST00000696058.1:c.896T>G

ENST00000696059.1:c.*844T>G

ENST00000696060.1:c.968T>G

ENST00000696061.1:c.896T>G

ENST00000696062.1:c.962T>G

ENST00000696063.1:c.974T>G

ENST00000696064.1:c.746T>G

ENST00000696065.1:c.221T>G

ENST00000696072.1:n.254T>G

ENST00000696073.1:n.1210T>G

ENST00000696074.1:n.450T>G

ENST00000696075.1:c.*869T>G

ENST00000696076.1:c.968T>G

ENST00000696077.1:c.893T>G

ENST00000696078.1:c.896T>G

ENST00000696079.1:c.896T>G

ENST00000696080.1:c.899T>G

ENST00000696081.1:n.1018T>G

ENST00000696082.1:c.974T>G

ENST00000696083.1:n.1856T>G

ENST00000696084.1:n.1076T>G

ENST00000696104.1:c.583T>G

ENST00000372874.9:c.899T>G

ENST00000372874.8:c.899T>G

ENST00000372887.5:c.152-2839A>C

ENST00000464097.5:n.649T>G

ENST00000492931.5:n.1059T>G

ENST00000536532.5:c.*42T>G

ENST00000537820.1:c.827T>G

ENST00000539235.5:c.*283T>G

NM_000022.2:c.899T>G

NM_000022.3:c.899T>G

NM_001322050.1:c.494T>G

NM_001322051.1:c.827T>G

NR_136160.1:n.985T>G

NM_001322050.2:c.494T>G

NM_001322051.2:c.827T>G

NR_136160.2:n.926T>G

Uncertain Significance

PM2_Supporting

PM5 BS3 BS2 PS3 PS1

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 ADA 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.899T>G (NM_000022.4) variant in ADA is a missense variant predicted to cause substitution of Phenylalanine by Cysteine at amino acid 300 (p.Phe300Cys). The filtering allele frequency (the upper threshold of the 95% CI of 64/1180048) of the c.899T>G variant in ADA is 0.00004346 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD. To our knowledge, this variant has not been reported in the literature in individuals affected with ADA-related conditions or in functional studies. Due to insufficient evidence, this variant is classified as a variant of uncertain significance for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): PM2_Supporting.

PM2_Supporting

The filtering allele frequency (the upper threshold of the 95% CI of 64/1180048) of the c.899T>G variant in ADA is 0.00004346 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0001742) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). No homozygotes have been observed in gnomAD.

PM5