Submissions for variant NM_198053.3(CD247):c.301C>T (p.Gln101Ter)

gnomAD frequency: 0.00021  dbSNP: rs55729925

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000482496	SCV000566899	pathogenic	not provided	2015-06-23	criteria provided, single submitter	clinical testing	The Q101X nonsense variant in the CD3Z gene is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The Q101X variant was not observed at any significant frequency in approximately 8,600 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. Therefore, we consider this variant to be pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV000762860	SCV000893224	likely pathogenic	Immunodeficiency 25	2018-10-31	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000762860	SCV000936004	pathogenic	Immunodeficiency 25	2023-12-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln101*) in the CD247 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CD247 are known to be pathogenic (PMID: 17170122, 26542031). This variant is present in population databases (rs55729925, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with CD247-related conditions. ClinVar contains an entry for this variant (Variation ID: 419227). For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004586729	SCV005076576	pathogenic	Severe combined immunodeficiency disease	2024-04-30	criteria provided, single submitter	clinical testing	Variant summary: CD247 c.301C>T (p.Gln101X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 0.00026 in 250742 control chromosomes in the gnomAD database, including 1 homozygotes. This frequency is not significantly higher than estimated for a pathogenic variant in CD247 causing Severe Combined Immunodeficiency (0.00026 vs 0.00035), allowing no conclusion about variant significance. c.301C>T has been reported in the literature in individuals affected with Primary immunodeficiencies (examples: Gallo_2016 and Rudilla_2019). The following publications have been ascertained in the context of this evaluation (PMID: 27872624, 31681265). ClinVar contains an entry for this variant (Variation ID: 419227). Based on the evidence outlined above, the variant was classified as pathogenic.
PreventionGenetics, part of Exact Sciences	RCV003962333	SCV004785756	likely pathogenic	CD247-related disorder	2024-08-22	no assertion criteria provided	clinical testing	The CD247 c.301C>T variant is predicted to result in premature protein termination (p.Gln101*). This variant was reported in the heterozygous state, and interpreted as pathogenic, in individuals undergoing preconception carrier screening analyses (Supplementary Table 001, Capalbo et al. 2019. PubMed ID: 31589614). This variant is reported in 0.068% of alleles in individuals of European (Finnish) descent in gnomAD. Nonsense variants in CD247 are expected to be pathogenic. This variant is interpreted as likely pathogenic.