Evidence Repository
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_000215.4(JAK3):c.2636A>G (p.His879Arg)

CA9301563

372390 (ClinVar)

Gene: JAK3
Condition: T-B+ severe combined immunodeficiency due to JAK3 deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 795cc53a-7c8f-4cc6-a41e-ce433d0ed652
Approved on: 2024-01-17
Published on: 2024-01-17

HGVS expressions

NM_000215.4:c.2636A>G
NM_000215.4(JAK3):c.2636A>G (p.His879Arg)
NC_000019.10:g.17832563T>C
CM000681.2:g.17832563T>C
NC_000019.9:g.17943372T>C
CM000681.1:g.17943372T>C
NC_000019.8:g.17804372T>C
NG_007273.1:g.20429A>G
ENST00000458235.7:c.2636A>G
ENST00000458235.5:c.2636A>G
ENST00000527031.5:n.2278+4164A>G
ENST00000527670.5:c.2636A>G
ENST00000534444.1:c.2636A>G
NM_000215.3:c.2636A>G

Likely Benign

Met criteria codes 1
BS1
Not Met criteria codes 8
BS2 BS3 PS3 PS1 PP4 PM3 PM1 PM5

Evidence Links 0

Expert Panel

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 c.2636A>G (NM_000215.4) variant in JAK3 is a missense variant predicted to cause substitution of Histidine by Arginine at amino acid 879 (p.His879Arg). The filtering allele frequency (the lower threshold of the 95% CI of 63/24964) of the c.2636A>G variant in JAK3 is 0.001911 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold (>0.00100) for BS1, and therefore meets this criterion (BS1). To our knowledge, this variant has not been reported in the literature in individuals affected with JAK3-related conditions. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BS1. (VCEP specifications version 1).
Met criteria codes
BS1
The filtering allele frequency (the lower threshold of the 95% CI of 63/24964) of the c.2636A>G variant in JAK3 is 0.001911 for African/African American chromosomes by gnomAD v2.1.1, which is higher than the ClinGen SCID VCEP threshold (>0.00100) for BS1, and therefore meets this criterion (BS1).
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
BS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PS3
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
PP4
To our knowledge, this variant has not been reported in the literature in individuals affected with JAK3-related conditions.
PM3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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