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]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000215.4(JAK3):c.2323C>T (p.Arg775Cys)

CA160228

134574 (ClinVar)

Gene: JAK3
Condition: T-B+ severe combined immunodeficiency due to JAK3 deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 786ceb58-2316-4c3c-877d-1e27b487e669
Approved on: 2024-04-03
Published on: 2024-04-03

HGVS expressions

NM_000215.4:c.2323C>T
NM_000215.4(JAK3):c.2323C>T (p.Arg775Cys)
NC_000019.10:g.17834598G>A
CM000681.2:g.17834598G>A
NC_000019.9:g.17945407G>A
CM000681.1:g.17945407G>A
NC_000019.8:g.17806407G>A
NG_007273.1:g.18394C>T
ENST00000526008.6:c.*880C>T
ENST00000696967.1:n.1500C>T
ENST00000696970.1:n.978C>T
ENST00000458235.7:c.2323C>T
ENST00000458235.5:c.2323C>T
ENST00000527031.5:n.2278+2129C>T
ENST00000527670.5:c.2323C>T
ENST00000534444.1:c.2323C>T
NM_000215.3:c.2323C>T
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Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 3
BA1 PM5 BS1

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 NM_000215.4(JAK3):c.2324G>A variant in JAK3 is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 775 (p.Arg775Cys). The filtering allele frequency (the upper threshold of the 95% CI of 55/1113096) of the c.2323C>T variant in JAK3 is 0.00003886 for European (non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID JAK3 VCEP threshold (<0.000115) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance 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: PM2_Supporting (VCEP specifications version 1).
Met criteria codes
PM2_Supporting
The filtering allele frequency (the upper threshold of the 95% CI of 55/1113096) of the c.2323C>T variant in JAK3 is [0.00003886] for European (non-Finnish) chromosomes by gnomAD v 4.0.0, which is lower than the ClinGen SCID JAK3 VCEP threshold([ <0.000115]) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).
Not Met criteria codes
BA1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
PM5
p.R775H classified as VUS (2S+1M)
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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