Submissions for variant NM_001242.5(CD27):c.778C>T (p.Pro260Ser)

gnomAD frequency: 0.00007  dbSNP: rs752860747

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001202894	SCV001374028	uncertain significance	Lymphoproliferative syndrome 2	2022-08-29	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 260 of the CD27 protein (p.Pro260Ser). 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: 934493). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics	RCV004033552	SCV004921354	uncertain significance	Inborn genetic diseases	2024-01-30	criteria provided, single submitter	clinical testing	The c.778C>T (p.P260S) alteration is located in exon 6 (coding exon 6) of the CD27 gene. This alteration results from a C to T substitution at nucleotide position 778, causing the proline (P) at amino acid position 260 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004690008	SCV005185973	uncertain significance	not specified	2024-05-03	criteria provided, single submitter	clinical testing	Variant summary: CD27 c.778C>T (p.Pro260Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 249110 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.778C>T in individuals affected with Lymphoproliferative Syndrome 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 934493). Based on the evidence outlined above, the variant was classified as uncertain significance.