ClinVar

This variant, formerly titled SEVERE COMBINED IMMUNODEFICIENCY, AUTOSOMAL RECESSIVE, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-POSITIVE, has been reclassified as a variant of unknown significance based on a review of the ExAC database by Hamosh (2018).

In a male infant (patient 1) with a primary immunodeficiency presenting as T-, B+, NK+ SCID, Puel et al. (1998) identified 2 homozygous variants in the IL7R gene: a C-to-T transition in exon 2, resulting in a thr66-to-ile (T66I) substitution, and an A-to-G transition in exon 4, resulting in an ile138-to-val (I138V; 146661.0002) substitution. The patient was homozygous and both parents were heterozygous for both variants. Each parent expressed mRNA only from the wildtype allele, and IL7R mRNA was undetectable in patient cells. However, functional studies of these variants did not reveal significant defects and the variants were present in healthy controls, indicating that T66I and I138V represent polymorphisms and were not responsible for the disease.

Hamosh (2018) found that the T (minor) allele of this variant was present in 76,179 of 121,330 alleles in the ExAC database, for an allele frequency of 0.6279 (April 20, 2018), suggesting that the variant is not pathogenic.

In the patient (patient 1) with a primary immunodeficiency manifest as T-, B+, NK+ SCID (IMD104; 608971) reported by Puel et al. (1998), Puel and Leonard (2000) identified a homozygous splice site mutation (146661.0007) in the IL7R gene that was responsible for the disorder. Each unaffected parent was heterozygous for the splice site mutation. Patient cells showed no detectable IL7R mRNA, consistent with complete IL7R deficiency.