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_000022.2(ADA):c.22G>A (p.Asp8Asn)

CA115289

1973 (ClinVar)

Gene: N/A

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 89074206-c4a1-4f51-9071-c651840148ce

HGVS expressions

NM_000022.2(ADA):c.22G>A (p.Asp8Asn)

NC_000020.11:g.44651586C>T

CM000682.2:g.44651586C>T

NC_000020.10:g.43280227C>T

CM000682.1:g.43280227C>T

NC_000020.9:g.42713641C>T

NG_007385.1:g.5150G>A

ENST00000372874.9:c.22G>A

ENST00000372874.8:c.22G>A

ENST00000492931.5:n.106G>A

ENST00000535573.1:n.332+316G>A

ENST00000536076.1:n.213+316G>A

ENST00000536532.5:c.22G>A

ENST00000537820.1:c.22G>A

ENST00000539235.5:c.22G>A

ENST00000545776.5:n.76G>A

NM_000022.2:c.22G>A

NM_000022.3:c.22G>A

NM_001322050.1:c.-268G>A

NM_001322051.1:c.22G>A

NR_136160.1:n.173G>A

NM_000022.4:c.22G>A

NM_001322050.2:c.-268G>A

NM_001322051.2:c.22G>A

NR_136160.2:n.114G>A

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_000022.2:c.22G>A variant in ADA is a missense variant predicted to cause substitution of aspartic acid by asparagine at amino acid 8 (p.Asp8Asn). This variant is present at an overall minor allele frequency of 0.05863 (10050/171418 alleles) with the highest population minor allele frequency of 0.1300 (3033/23322) in the South Asian population in gnomAD v2.1.1. This frequency is higher than the ClinGen SCID VCEP's threshold for BA1 (>0.00721); therefore, BA1 is met. This variant has been observed in 434 homozygous individuals in gnomAD, 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 (SCID VCEP specifications version 1.0).

BS2_Supporting

This variant has been observed in 434 homozygous individuals in gnomAD, a condition with full penetrance at an early age (BS2_Supporting).

BA1

Overall frequency in gnomAD is 0.05863 (10050/171418 alleles) and highest frequency is 0.1300 (3033/23322) in South Asian population. https://gnomad.broadinstitute.org/variant/20-43280227-C-T This is higher than the cutoff set for BA1 in the SCID VCEP's ADA specifications (gnomAD popmax filtering allele frequency > 0.00721. There are also 434 homozygotes in gnomAD. Therefore, BA1 applies.

Approved on: 2024-01-23

Published on: 2024-01-23

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