Evidence Repository
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.736C>T (p.Gln246Ter)

CA409120239

549915 (ClinVar)

Gene: ADA
Condition: adenosine deaminase deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: ea0a6057-1873-4413-9acd-7ccbc79ce6fa
Approved on: 2024-01-24
Published on: 2024-01-24

HGVS expressions

NM_000022.4:c.736C>T
NM_000022.4(ADA):c.736C>T (p.Gln246Ter)
NC_000020.11:g.44622873G>A
CM000682.2:g.44622873G>A
NC_000020.10:g.43251514G>A
CM000682.1:g.43251514G>A
NC_000020.9:g.42684928G>A
NG_007385.1:g.33863C>T
ENST00000372874.9:c.736C>T
ENST00000372874.8:c.736C>T
ENST00000372887.5:c.152-1060G>A
ENST00000464097.5:n.486C>T
ENST00000492931.5:n.896C>T
ENST00000536532.5:c.736C>T
ENST00000537820.1:c.664C>T
ENST00000539235.5:c.*120C>T
NM_000022.2:c.736C>T
NM_000022.3:c.736C>T
NM_001322050.1:c.331C>T
NM_001322051.1:c.664C>T
NR_136160.1:n.887C>T
NM_001322050.2:c.331C>T
NM_001322051.2:c.664C>T
NR_136160.2:n.828C>T
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Pathogenic

Met criteria codes 3
PVS1 PM2_Supporting PM3_Supporting

Evidence Links 0

Expert Panel

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.736C>T (p.Gln246Ter)(NM_000022.4) variant in ADA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 8/12 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1_Met). The variant is absent in gnomAD v4 (PM2_Supporting). One patient (U444) was found homozygous for this mutation (PMID: 17185467,PM3_Supporting).Based on the above evidence, this variant can be classified as pathogenic for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP(specification version 1.0): PVS1_Met,PM2_Supporting,PM3_Supporting.
Met criteria codes
PVS1
The c.736C>T (p.Gln246Ter)(NM_000022.4) variant in ADA is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 8/12 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1_met).
PM2_Supporting
The variant is absent in gnomAD v4 (PM2_Supporting)
PM3_Supporting
One patient (U444) was found homozygous for this mutation (PMID: 17185467,PM3_Supporting)
Curation History
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