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.175A>T (p.Lys59Ter)

CA404774961

1999662 (ClinVar)

Gene: JAK3 (HGNC:3718)

Condition: T-B+ severe combined immunodeficiency due to JAK3 deficiency (MONDO:0010938)

Inheritance Mode: Autosomal recessive inheritance

UUID: c9a1f1b7-afee-4d26-857e-d590482331f7

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000215.4:c.175A>T

NM_000215.4(JAK3):c.175A>T (p.Lys59Ter)

NC_000019.10:g.17844243T>A

CM000681.2:g.17844243T>A

NC_000019.9:g.17955052T>A

CM000681.1:g.17955052T>A

NC_000019.8:g.17816052T>A

NG_007273.1:g.8749A>T

ENST00000458235.7:c.175A>T

ENST00000458235.5:c.175A>T

ENST00000526008.5:n.275A>T

ENST00000527031.5:n.265A>T

ENST00000527670.5:c.175A>T

ENST00000528293.1:n.314A>T

ENST00000534444.1:c.175A>T

NM_000215.3:c.175A>T

Likely Pathogenic

PVS1 PM2_Supporting

PM5 BA1 BS1 PS1

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.175A>T (p.Lys59Ter) variant in JAK3 is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 2/24 leading to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). This variant is absent from gnomAD v2.1.1 (PM2_Supporting). To our knowledge, this variant has not been reported in the literature in individuals affected with JAK3-related conditions, and functional studies have not been found. In summary, this variant meets the criteria to be classified as Likely Pathogenic for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: PVS1 and PM2_supporting. (VCEP specifications version 1).

PVS1

PM2_Supporting

This variant is absent from gnomAD v2.1.1 (PM2_Supporting).

PM5

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

BA1

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

BS1

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

PS1

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

Curation History

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