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.631C>T (p.Arg211Cys)

CA115285

1966 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 4f92adc5-3431-4f25-8298-d4cd9bfea5a6

HGVS expressions

NM_000022.4:c.631C>T

NM_000022.4(ADA):c.631C>T (p.Arg211Cys)

NC_000020.11:g.44623054G>A

CM000682.2:g.44623054G>A

NC_000020.10:g.43251695G>A

CM000682.1:g.43251695G>A

NC_000020.9:g.42685109G>A

NG_007385.1:g.33682C>T

ENST00000372874.9:c.631C>T

ENST00000372874.8:c.631C>T

ENST00000372887.5:c.152-879G>A

ENST00000464097.5:n.305C>T

ENST00000492931.5:n.715C>T

ENST00000536532.5:c.631C>T

ENST00000537820.1:c.607-124C>T

ENST00000539235.5:c.*15C>T

NM_000022.2:c.631C>T

NM_000022.3:c.631C>T

NM_001322050.1:c.226C>T

NM_001322051.1:c.607-124C>T

NR_136160.1:n.782C>T

NM_001322050.2:c.226C>T

NM_001322051.2:c.607-124C>T

NR_136160.2:n.723C>T

Likely Pathogenic

PP1_Moderate PM3 PM5

PM2

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.631C>T is a missense variant predicted to cause substitution of Arginine by Cysteine at amino acid 211 (p. Arg211Cys). The highest population minor allele frequency in gnomAD v4 is 0.0005167 (31/60000) in Admixed American population (PM2_Supporting, BS1, and BA1 are not met). The variant has been reported to segregate with SCID in 2 affected family members from 1 family (PP1_moderate; PMID :8051429). Patient was found heterozygous for R211C & L107P which is classified as likely pathogenic by SCID VCEP (1 pt.) (PM3) (PMID: 2166947).Another missense variant [c.632G>A, p.Arg211His)] in the same codon has been classified as pathogenic for SCID by the ClinGen SCID VCEP (PM5). In summary, this variant meets the criteria to be classified as a Likely Pathogenic variant for autosomal recessive severe combined immunodeficiency due to ADA deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PP1_moderate,PM3,PM5(VCEP specifications version 1).

PP1_Moderate

The variant has been reported to segregate with SCID in 2 affected family members from 1 family (PP1_moderate; PMID: 8051429)

PM3

Patient was found heterozygous for R211C & L107P which is classified as likely pathogenic by SCID VCEP (1 pt.) (PM3) (PMID: 2166947)

PM5

Another missense variant [c.632G>A, p.Arg211His)] in the same codon has been classified as pathogenic for SCID by the ClinGen SCID VCEP (PM5).

PM2

The highest population minor allele frequency in gnomAD v4 is 0.0005167 (31/60000) in Admixed American population. (PM2_Supporting, BS1, and BA1 are not met)

Approved on: 2024-01-10

Published on: 2024-01-10

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