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_000022.4(ADA):c.539T>C (p.Ile180Thr)

CA409120875

1696220 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 15bc8ce9-12b2-4478-b5b1-7b09e608007d

HGVS expressions

NM_000022.4:c.539T>C

NM_000022.4(ADA):c.539T>C (p.Ile180Thr)

NC_000020.11:g.44624269A>G

CM000682.2:g.44624269A>G

NC_000020.10:g.43252910A>G

CM000682.1:g.43252910A>G

NC_000020.9:g.42686324A>G

NG_007385.1:g.32467T>C

ENST00000492931.6:n.630T>C

ENST00000536076.2:c.386T>C

ENST00000536532.6:c.539T>C

ENST00000537820.2:c.539T>C

ENST00000539235.6:c.219-1191T>C

ENST00000695889.1:c.219-1339T>C

ENST00000695890.1:n.2342T>C

ENST00000695891.1:c.219-1339T>C

ENST00000695927.1:c.617T>C

ENST00000695949.1:c.536T>C

ENST00000695957.1:c.*30T>C

ENST00000695991.1:c.217-1339T>C

ENST00000695992.1:c.539T>C

ENST00000695993.1:c.539T>C

ENST00000695994.1:c.539T>C

ENST00000695995.1:c.217-1191T>C

ENST00000695996.1:n.610T>C

ENST00000695997.1:n.494T>C

ENST00000696003.1:n.631T>C

ENST00000696004.1:n.631T>C

ENST00000696005.1:c.61T>C

ENST00000696006.1:c.539T>C

ENST00000696007.1:c.390T>C

ENST00000696008.1:n.1694T>C

ENST00000696009.1:n.1889T>C

ENST00000696017.1:c.536T>C

ENST00000696034.1:c.539T>C

ENST00000696035.1:n.649T>C

ENST00000696036.1:n.1229T>C

ENST00000696037.1:n.2216T>C

ENST00000696038.1:c.*285T>C

ENST00000696039.1:n.827T>C

ENST00000696058.1:c.539T>C

ENST00000696059.1:c.*484T>C

ENST00000696060.1:c.539T>C

ENST00000696061.1:c.536T>C

ENST00000696062.1:c.602T>C

ENST00000696063.1:c.614T>C

ENST00000696064.1:c.386T>C

ENST00000696065.1:c.66-1339T>C

ENST00000696074.1:n.155T>C

ENST00000696075.1:c.*509T>C

ENST00000696076.1:c.539T>C

ENST00000696077.1:c.536T>C

ENST00000696078.1:c.539T>C

ENST00000696079.1:c.539T>C

ENST00000696080.1:c.539T>C

ENST00000696081.1:n.658T>C

ENST00000696082.1:c.617T>C

ENST00000696083.1:n.1420T>C

ENST00000696084.1:n.640T>C

ENST00000696104.1:c.363-1339T>C

ENST00000696105.1:c.*80T>C

ENST00000372874.9:c.539T>C

ENST00000372874.8:c.539T>C

ENST00000464097.5:n.213T>C

ENST00000492931.5:n.623T>C

ENST00000536532.5:c.539T>C

ENST00000537820.1:c.539T>C

ENST00000539235.5:c.219-1191T>C

NM_000022.2:c.539T>C

NM_000022.3:c.539T>C

NM_001322050.1:c.134T>C

NM_001322051.1:c.539T>C

NR_136160.1:n.690T>C

NM_001322050.2:c.134T>C

NM_001322051.2:c.539T>C

NR_136160.2:n.631T>C

Uncertain Significance

PM2_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 ADA Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000022.4 :c.539T>C is a missense variant predicted to cause substitution of Isoleucine by Threonine at amino acid 180 (p.Ile180Thr).The filtering allele frequency (the upper threshold of the 95% CI of 6/91086) of the c.539T>C variant in ADA is 0.00002995 for South Asian 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). There are no publications for this variant in the literature. Based on insufficient evidence, this variant may be classified as 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 6/91086) of the c.539T>C variant in ADA is 0.00002995 for South Asian 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).

Approved on: 2024-05-01

Published on: 2024-05-01

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