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: NM_000022.4(ADA):c.425G>A (p.Arg142Gln)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA266009

68262 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 0bf86526-9d24-4027-b0fa-f37b88888f3c

Approved on: 2024-01-10

Published on: 2024-01-10

HGVS expressions

NM_000022.4:c.425G>A

NM_000022.4(ADA):c.425G>A (p.Arg142Gln)

NC_000020.11:g.44625622C>T

CM000682.2:g.44625622C>T

NC_000020.10:g.43254263C>T

CM000682.1:g.43254263C>T

NC_000020.9:g.42687677C>T

NG_007385.1:g.31114G>A

ENST00000372874.9:c.425G>A

ENST00000372874.8:c.425G>A

ENST00000464097.5:n.99G>A

ENST00000492931.5:n.509G>A

ENST00000536532.5:c.425G>A

ENST00000537820.1:c.425G>A

ENST00000539235.5:c.219-2544G>A

NM_000022.2:c.425G>A

NM_000022.3:c.425G>A

NM_001322050.1:c.73+834G>A

NM_001322051.1:c.425G>A

NR_136160.1:n.576G>A

NM_001322050.2:c.73+834G>A

NM_001322051.2:c.425G>A

NR_136160.2:n.517G>A

Benign

BA1 BS2_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(ADA):c.425G>A is a missense variant predicted to cause substitution of Arginine by Glutamine at amino acid 142 (p.Arg142Gln). The filtering allele frequency (the upper threshold of the 95% CI of 975/74574 alleles) of the c.425G>A variant in ADA is 0.01222 for African/African American chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00721) for BA1 and therefore meets this criterion (BA1). This variant has been observed in 6 homozygous individuals in gnomAD v.4, a condition with full penetrance at an early age (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1).

BA1

The filtering allele frequency (the upper threshold of the 95% CI of 975/74574 alleles) of the c.425G>A variant in ADA is 0.01222 for African/African American chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00721) for BA1 and therefore meets this criterion (BA1).

BS2_Supporting

This variant has been observed in 6 homozygous individuals in gnomAD v.4, a condition with full penetrance at an early age (BS2_Supporting).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.