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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000215.4(JAK3):c.2773C>A (p.Arg925Ser)

CA9301512

418267 (ClinVar)

Gene: JAK3

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

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b4687fba-0d80-4e07-a97a-fba3429940df

HGVS expressions

NM_000215.4:c.2773C>A

NM_000215.4(JAK3):c.2773C>A (p.Arg925Ser)

NC_000019.10:g.17831706G>T

CM000681.2:g.17831706G>T

NC_000019.9:g.17942515G>T

CM000681.1:g.17942515G>T

NC_000019.8:g.17803515G>T

NG_007273.1:g.21286C>A

ENST00000458235.7:c.2773C>A

ENST00000458235.5:c.2773C>A

ENST00000527031.5:n.2278+5021C>A

ENST00000527670.5:c.2773C>A

ENST00000534444.1:c.2773C>A

NM_000215.3:c.2773C>A

Likely Benign

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.2773C>A (p.Arg925Ser) missense variant has a popmax filtering allele frequency in gnomAD v2.1.1 is 0.002278 (based on 94/34558 alleles in the Latino/Admixed American population), which is above the ClinGen SCID VCEP threshold of >0.00100 (BS1). To our knowledge, the variant has not been reported in a SCID patient in the literature. In summary, this variant meets the criteria to be classified as Likely Benign for autosomal recessive T-B+ SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP. Criteria applied: BS1 (VCEP specifications version 1).

BS1

The popmax filtering allele frequency in gnomAD v2.1.1 is 0.002278 (based on 94/34558 alleles in the Latino/Admixed American population), which is above the ClinGen SCID VCEP threshold of >0.00100 (BS1).

Approved on: 2024-01-17

Published on: 2024-01-17

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.