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]

Variant: NR_136160.2:n.94T>G

CA409122633

2709658 (ClinVar)

Gene: ADA (HGNC:100)

Condition: severe combined immunodeficiency (MONDO:0015974)

Inheritance Mode: Autosomal recessive inheritance

UUID: c188c8c2-bf2f-422a-9a17-d5193d2ed908

Approved on: 2026-03-26

Published on: 2026-03-26

HGVS expressions

NR_136160.2:n.94T>G

NC_000020.11:g.44651606A>C

CM000682.2:g.44651606A>C

NC_000020.10:g.43280247A>C

CM000682.1:g.43280247A>C

NC_000020.9:g.42713661A>C

NG_007385.1:g.5130T>G

ENST00000492931.6:n.93T>G

ENST00000536076.2:c.-121+296T>G

ENST00000536532.6:c.2T>G

ENST00000537820.2:c.2T>G

ENST00000539235.6:c.2T>G

ENST00000695889.1:c.2T>G

ENST00000695891.1:c.2T>G

ENST00000695949.1:c.2T>G

ENST00000695957.1:c.2T>G

ENST00000695991.1:c.2T>G

ENST00000695992.1:c.2T>G

ENST00000695993.1:c.2T>G

ENST00000695994.1:c.2T>G

ENST00000695995.1:c.2T>G

ENST00000695996.1:n.73T>G

ENST00000695997.1:n.73T>G

ENST00000696003.1:n.94T>G

ENST00000696004.1:n.94T>G

ENST00000696006.1:c.2T>G

ENST00000696009.1:n.113T>G

ENST00000696010.1:n.115T>G

ENST00000696017.1:c.2T>G

ENST00000696034.1:c.2T>G

ENST00000696038.1:c.2T>G

ENST00000696039.1:n.321+296T>G

ENST00000696058.1:c.2T>G

ENST00000696059.1:c.2T>G

ENST00000696060.1:c.2T>G

ENST00000696061.1:c.2T>G

ENST00000696062.1:c.96+494T>G

ENST00000696063.1:c.2T>G

ENST00000696064.1:c.-118+296T>G

ENST00000696065.1:c.-121+296T>G

ENST00000696075.1:c.2T>G

ENST00000696076.1:c.2T>G

ENST00000696077.1:c.2T>G

ENST00000696078.1:c.2T>G

ENST00000696079.1:c.2T>G

ENST00000696080.1:c.2T>G

ENST00000696084.1:n.103T>G

ENST00000696104.1:c.2T>G

ENST00000696105.1:c.2T>G

ENST00000372874.9:c.2T>G

ENST00000372874.8:c.2T>G

ENST00000492931.5:n.86T>G

ENST00000535573.1:n.332+296T>G

ENST00000536076.1:n.213+296T>G

ENST00000536532.5:c.2T>G

ENST00000537820.1:c.2T>G

ENST00000539235.5:c.2T>G

ENST00000545776.5:n.56T>G

NM_000022.2:c.2T>G

NM_000022.3:c.2T>G

NM_001322050.1:c.-288T>G

NM_001322051.1:c.2T>G

NR_136160.1:n.153T>G

NM_000022.4:c.2T>G

NM_001322050.2:c.-288T>G

NM_001322051.2:c.2T>G

Uncertain Significance

PS3_Moderate PVS1_Moderate PM2_Supporting

PS1 PM5

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 2.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The NM_000022.4(ADA):c.2T>G is a missense variant predicted to cause substitution of Methionine by Arginine at amino acid 1 (p.Met1Arg). This sequence change affects the initiator methionine of the ADA mRNA. The next possible initiation codon is at codon 52. This variant is absent from gnomAD v4.1.0, good coverage (PM2_supporting). The NM_000022.4:c.2T>G variant in ADA may cause a truncated or absent protein by altering the start codon of the coding sequence and is predicted to lead to the omission of a critical region of the protein (PVS1_Moderate). ADA enzyme activity assay in E. coli S3834 showed 0.01% of wild-type activity for the p.Met1Arg variant, indicating severely reduced protein function consistent with loss of function (PS3_Moderate). In summary, this variant meets the criteria to be classified as uncertain significance for SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen ClinGen SCID-VCEP: PM2_supporting, PVS1_moderate, PS3_moderate. (VCEP specifications version 2.1.0).

PS3_Moderate

ADA enzyme activity assay in E. coli S3834 showed 0.01% of wild-type activity for the p.Met1Arg variant, indicating severely reduced protein function consistent with loss of function (PS3_Moderate).

PVS1_Moderate

The NM_000022.4:c.2T>G (p.Met1?) variant in ADA may cause a truncated or absent protein by altering the start codon of the coding sequence and is predicted to lead to the omission of a critical region of the protein (PVS1_Moderate).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 good coverage (PM2_supporting)

PS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

PM5

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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