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_000215.4(JAK3):c.2164G>A (p.Val722Ile)

CA160225

134573 (ClinVar)

Gene: JAK3

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

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: a8274608-4e6d-42b9-a92a-a14282ba2d2a

HGVS expressions

NM_000215.4:c.2164G>A

NM_000215.4(JAK3):c.2164G>A (p.Val722Ile)

NC_000019.10:g.17834887C>T

CM000681.2:g.17834887C>T

NC_000019.9:g.17945696C>T

CM000681.1:g.17945696C>T

NC_000019.8:g.17806696C>T

NG_007273.1:g.18105G>A

ENST00000526008.6:c.*721G>A

ENST00000696967.1:n.1341G>A

ENST00000696970.1:n.819G>A

ENST00000458235.7:c.2164G>A

ENST00000458235.5:c.2164G>A

ENST00000527031.5:n.2278+1840G>A

ENST00000527670.5:c.2164G>A

ENST00000534444.1:c.2164G>A

NM_000215.3:c.2164G>A

Benign

BA1 BS2_Supporting

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

NM_000215.4(JAK3):c.2164G>A is a missense variant predicted to cause substitution of Valine by Isoleucine at amino acid 722 (p.Val722Ile). The filtering allele frequency (the lower threshold of the 95% CI of 12957/1180016) of the c.2164G>A variant in JAK3 is 0.01082 for European (non-Finnish) chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00447) for BA1, and therefore meets this criterion (BA1). Additionally, 120 adult homozygous occurrences are reported in gnomAD v4 (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive severe combined immunodeficiency due to JAK3 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BA1 and B2_Supporting (VCEP specifications version 1).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 12957/1180016) of the c.2164G>A variant in JAK3 is 0.01082 for European (non-Finnish) chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00447) for BA1, and therefore meets this criterion (BA1).

BS2_Supporting

Additionally, 120 adult homozygous occurrences are reported in gnomAD v4 (BS2_Supporting).

Approved on: 2024-04-03

Published on: 2024-04-03

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