Submissions for variant NM_001242.5(CD27):c.721G>A (p.Glu241Lys)

gnomAD frequency: 0.00003  dbSNP: rs759504816

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000812609	SCV000952928	uncertain significance	Lymphoproliferative syndrome 2	2023-12-22	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 241 of the CD27 protein (p.Glu241Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with CD27-related conditions. ClinVar contains an entry for this variant (Variation ID: 656240). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV004768683	SCV005379956	uncertain significance	not provided	2023-12-18	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genetic Services Laboratory, University of Chicago	RCV003151157	SCV003839322	uncertain significance	not specified	2022-06-09	no assertion criteria provided	clinical testing	DNA sequence analysis of the CD27 gene demonstrated a sequence change, c.721G>A, in exon 6 that results in an amino acid change, p.Glu241Lys. This sequence change does not appear to have been previously described in individuals with CD27-related disorders. This sequence change has been described in the gnomAD database with a frequency of 0.14479% in the Ashkenazi Jewish subpopulation (dbSNP rs759504816). The p.Glu241Lys change affects a highly conserved amino acid residue located in a domain of the CD27 protein that is known to be functional. In-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL) provide contradictory results for the p.Glu241Lys substitution. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Glu241Lys change remains unknown at this time.