ClinVar Miner

Submissions for variant NM_002185.5(IL7R):c.394C>T (p.Pro132Ser)

dbSNP: rs104893894
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen RCV000015968 SCV004810400 likely pathogenic Immunodeficiency 104 2024-01-24 reviewed by expert panel curation NM_002185.5(IL7R):c.394C>T is a missense variant predicted to cause substitution of Proline by Serine at amino acid 132 (p.Pro132Ser). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00002236 (1/44718) in Admixed American population which is lower than the ClinGen SCID VCEP threshold (<0.00004129) for PM2_Supporting, meeting this criterion (PM2_Supporting). 3 patients (PMID: 11023514) were found homozygous for this mutation (1 pt.) (PM3_met). 2 patients (Pt. 85 and 86) were found homozygous for this mutation in a consanguineous family (PMID : 35482138). 3 patients with SCID (0.5 pt.), genome sequencing conducted (0.5 pt.),T-B+NK+ lymphocyte subset profile (0.25 pt.) (Total : 1.25 pts) (PMID: 11023514,PP4_met). In response to IL-7 stimulation, Jak-3 phosphorylation was markedly reduced in both patient cells as well as in COS cells reconstituted with mutant IL-7R. (PMID: 11023514, PS3_supporting). The variant has been reported to segregate with SCID in 3 affected members from 2 families (PP1_strong). In summary, this variant meets the criteria to be classified as a Likely Pathogenic variant 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_met,PP4_met,PS3_supporting,PP1_strong(VCEP specifications version 1).
OMIM RCV000015968 SCV000036235 pathogenic Immunodeficiency 104 2000-10-15 no assertion criteria provided literature only

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