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]

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Variant: NM_000022.4(ADA):c.402C>T (p.Gly134=)

CA9871679

536186 (ClinVar)

Gene: ADA

Condition: adenosine deaminase deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 2cc1057b-9ac7-4d27-a0c7-0eab74eb6052

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000022.4:c.402C>T

NM_000022.4(ADA):c.402C>T (p.Gly134=)

NC_000020.11:g.44625645G>A

CM000682.2:g.44625645G>A

NC_000020.10:g.43254286G>A

CM000682.1:g.43254286G>A

NC_000020.9:g.42687700G>A

NG_007385.1:g.31091C>T

ENST00000372874.9:c.402C>T

ENST00000372874.8:c.402C>T

ENST00000464097.5:n.76C>T

ENST00000492931.5:n.486C>T

ENST00000536532.5:c.402C>T

ENST00000537820.1:c.402C>T

ENST00000539235.5:c.219-2567C>T

NM_000022.2:c.402C>T

NM_000022.3:c.402C>T

NM_001322050.1:c.73+811C>T

NM_001322051.1:c.402C>T

NR_136160.1:n.553C>T

NM_001322050.2:c.73+811C>T

NM_001322051.2:c.402C>T

NR_136160.2:n.494C>T

Likely Benign

BS1 BS2_Supporting BP7

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 c.402C>T (p.Gly134=) variant (NM_000022.4) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.003095 (89/19874 alleles) in African/African American population, which is higher than the ClinGen SCID VCEP threshold (>0.00161) for BS1, and therefore meets this criterion (BS1). In the gnomAD v2.1.1 database, this variant has been observed in 1 homozygous individual with no features of SCID, a condition with full penetrance at an early age. BS2_supporting is met. In summary, this variant is classified as a Likely Benign for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): BS1, BP7, and BS2_Supporting.

BS1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.003095 (89/19874 alleles) in African/African American population, which is higher than the ClinGen SCID VCEP threshold (>0.00161) for BS1, and therefore meets this criterion (BS1).

BS2_Supporting

In the gnomAD v2.1.1 database, this variant has been observed in 1 homozygous individual with no features of SCID, a condition with full penetrance at an early age. BS2_supporting is met.

BP7

The c.402C>T (p.Gly134=) variant (NM_000022.4) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7).

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