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_002185.5(IL7R):c.41T>C (p.Leu14Ser)

CA359425853

1683587 (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: e0a2dd66-32dc-4175-a9a7-5c38699e4566

Approved on: 2024-04-01

Published on: 2024-04-01

HGVS expressions

NM_002185.5:c.41T>C

NM_002185.5(IL7R):c.41T>C (p.Leu14Ser)

NC_000005.10:g.35857018T>C

CM000667.2:g.35857018T>C

NC_000005.9:g.35857120T>C

CM000667.1:g.35857120T>C

NC_000005.8:g.35892877T>C

NG_009567.1:g.5130T>C

ENST00000303115.8:c.41T>C

ENST00000303115.7:c.41T>C

ENST00000506850.5:c.41T>C

ENST00000508941.5:c.41T>C

ENST00000511031.1:n.217-3834T>C

ENST00000511982.1:c.41T>C

ENST00000514217.5:c.41T>C

ENST00000515665.1:c.41T>C

NM_002185.3:c.41T>C

NR_120485.1:n.144T>C

NM_002185.4:c.41T>C

NR_120485.2:n.170T>C

NR_120485.3:n.128T>C

Uncertain Significance

PP4 PM2_Supporting PM3_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 IL7R Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_002185.5(IL7R):c.41T>C is a missense variant predicted to cause substitution of Leucine by Serine at amino acid 14 (p.Leu14Ser). The highest population minor allele frequency in gnomAD v4 is 0.00001160 (1/86214 alleles) in South Asian population, which is lower than the ClinGen SCID VCEP threshold (<0.00004129) for PM2_Supporting, meeting this criterion (PM2_Supporting). Patient P1 was found homozygous for this mutation (0.5 pt.) (PM3_supporting) (PMID: 33599911).Patient with SCID (0.5 pt.) and exome sequencing conducted (0.5 pt.) (total :1 pt.) (PP4) (PMID: 33599911). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to IL7R deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM2_Supporting, PM3_supporting, PP4(VCEP specifications version 1).

PP4

Patient with SCID (0.5 pt.) and exome sequencing conducted (0.5 pt.) (total :1 pt.) (PP4) (PMID: 33599911)

PM2_Supporting

The highest population minor allele frequency in gnomAD v4 is 0.00001160 (1/86214 alleles) in South Asian population, which is lower than the ClinGen SCID VCEP threshold (<0.00004129) for PM2_Supporting, meeting this criterion (PM2_Supporting).

PM3_Supporting

Patient P1 was found homozygous for this mutation (0.5 pt.) (PM3_supporting) (PMID: 33599911)

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