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.239A>G (p.Lys80Arg)

CA251993

1954 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5adcbc29-0bdb-463d-ae7a-c6fb29411314

HGVS expressions

NM_000022.4:c.239A>G

NM_000022.4(ADA):c.239A>G (p.Lys80Arg)

NC_000020.11:g.44626579T>C

CM000682.2:g.44626579T>C

NC_000020.10:g.43255220T>C

CM000682.1:g.43255220T>C

NC_000020.9:g.42688634T>C

NG_007385.1:g.30157A>G

ENST00000372874.9:c.239A>G

ENST00000372874.8:c.239A>G

ENST00000492931.5:n.323A>G

ENST00000536076.1:n.419A>G

ENST00000536532.5:c.239A>G

ENST00000537820.1:c.239A>G

ENST00000539235.5:c.218+2468A>G

ENST00000545776.5:n.293A>G

NM_000022.2:c.239A>G

NM_000022.3:c.239A>G

NM_001322051.1:c.239A>G

NM_001322050.2:c.-51A>G

NM_001322051.2:c.239A>G

NR_136160.2:n.331A>G

Benign

BS2_Supporting BA1

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 NM_000022.4:c.239A>G variant in ADA is a missense variant predicted to cause substitution of lysine by arginine at amino acid 80 (p.Lys80Arg). The Popmax filtering allele frequency of this variant in the gnomAD v2.1.1 database is 0.06430, which is higher than the ClinGen SCID VCEP threshold (>0.00721) for BA1 (BA1). This variant has been observed in 551 homozygous individuals with no feature of SCID, a condition with full penetrance at an early age (BS2_Supporting). In summary, this variant meets the criteria to be classified as benign for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1).

BS2_Supporting

In the gnomAD v2.1.1 database, this variant has been observed in 551 homozygous individuals with no feature of SCID, a condition with full penetrance at an early age. BS2_Supporting is met.

BA1

The Popmax filtering allele frequency of this variant in the gnomAD v2.1.1 database is 0.06430, which is higher than the ClinGen SCID VCEP threshold (>0.00721) for BA1. Therefore BA1 is met.

Approved on: 2024-01-23

Published on: 2024-01-23

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