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]

Variant: NM_000215.4(JAK3):c.452C>G (p.Pro151Arg)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA160252

36422 (ClinVar)

Gene: JAK3

Condition: T-B+ severe combined immunodeficiency due to JAK3 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 1b8a4b35-8c5e-42d1-a036-34d2454bce11

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_000215.4:c.452C>G

NM_000215.4(JAK3):c.452C>G (p.Pro151Arg)

NC_000019.10:g.17843141G>C

CM000681.2:g.17843141G>C

NC_000019.9:g.17953950G>C

CM000681.1:g.17953950G>C

NC_000019.8:g.17814950G>C

NG_007273.1:g.9851C>G

ENST00000458235.7:c.452C>G

ENST00000458235.5:c.452C>G

ENST00000526008.5:n.552C>G

ENST00000527031.5:n.542C>G

ENST00000527670.5:c.452C>G

ENST00000528293.1:n.467C>G

ENST00000534444.1:c.452C>G

NM_000215.3:c.452C>G

Benign

BS2_Supporting BA1

BS1

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 JAK3 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_000215.4(JAK3):c.452C>G (p.Pro151Arg) variant in JAK3 is a missense variant predicted to cause the substitution of Proline by Arginine at amino acid 151 (p.Pro151Arg). The Popmax Filtering allele frequency (95% CI) of the variant is 0.008679 in gnomAD v.4 for European (non-Finnish) population 10486/1179548 alleles, which is higher than the ClinGen SCID VCEP threshold (>0.00447) for BA1, therefore, meets this criterion (BA1). Also, 59 homozygous adults are reported on GnomAD v2.1.1 (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive T-B+ severe combined immunodeficiency due to JAK3 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BA1 and BS2_Supporting (VCEP specifications version 1.0).

BS2_Supporting

59 homozygous adults are reported on GnomAD v.4 (BS2_Supporting).

BA1

The Popmax Filtering allele frequency (95% CI) of the variant is 0.008679 in gnomAD v.4 for European (non-Finnish) population 10486/1179548 alleles, which is higher than the ClinGen SCID VCEP threshold (>0.00447) for BA1, therefore, meets this criterion (BA1).

BS1

No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline

Curation History

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