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_002185.5(IL7R):c.265C>T (p.Gln89Ter)

CA3231898

804345 (ClinVar)

Gene: IL7R
Condition: severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-positive
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: 5974917f-d7a0-4bc5-9ebd-d4f8705d0724
Approved on: 2024-01-17
Published on: 2024-01-17

HGVS expressions

NM_002185.5:c.265C>T
NM_002185.5(IL7R):c.265C>T (p.Gln89Ter)
NC_000005.10:g.35867349C>T
CM000667.2:g.35867349C>T
NC_000005.9:g.35867451C>T
CM000667.1:g.35867451C>T
NC_000005.8:g.35903208C>T
NG_009567.1:g.15461C>T
ENST00000303115.8:c.265C>T
ENST00000303115.7:c.265C>T
ENST00000506850.5:c.265C>T
ENST00000511031.1:n.399C>T
ENST00000511982.1:c.265C>T
ENST00000514217.5:c.265C>T
NM_002185.3:c.265C>T
NR_120485.1:n.368C>T
NM_002185.4:c.265C>T
NR_120485.2:n.394C>T
NR_120485.3:n.352C>T

Likely Pathogenic

Met criteria codes 2
PVS1 PM2_Supporting
Not Met criteria codes 1
BS2

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 IL7R 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_002185.5(IL7R):c.265C>T (p.Gln89Ter) variant in IL7R is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 3/8, which is predicted to lead to nonsense-mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1). The filtering allele frequency based on the European (non-Finnish) population (upper bound of 95% CI of 3/113430 alleles) is 0.000007030 in gnomAD v2.1.1, which is below the SCID-VCEP threshold (<0.00004129; PM2_Supporting). This variant has been reported in ClinVar and LOVD without patient information; however, it has not been reported in the literature to our knowledge. 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, PM2_supporting (SCID VCEP specifications version 1.0).
Met criteria codes
PVS1
The NM_002185.5(IL7R):c.265C>T (p.Gln89Ter) variant in IL7R is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 3/8, which is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).
PM2_Supporting
The filtering allele frequency based on the European (non-Finnish) population (upper bound of 95% CI of 3/113430 observed alleles) is 0.000007030 in gnomAD v2.1.1 which is below the SCID-VCEP threshold (<0.00004129) and therefore meets this criterion (PM2_Supporting).
Not Met criteria codes
BS2
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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