Submissions for variant NM_058216.3(RAD51C):c.308_310del (p.Phe103del)

dbSNP: rs1064794253

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000480944	SCV000568393	uncertain significance	not provided	2022-04-25	criteria provided, single submitter	clinical testing	In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; Located in the critical ATPase domain (Miller 2004); Observed in an individual with a personal and/or family history of breast cancer (Thompson 2012); This variant is associated with the following publications: (PMID: 14704354, 21990120)
Ambry Genetics	RCV000569826	SCV000667134	uncertain significance	Hereditary cancer-predisposing syndrome	2022-05-05	criteria provided, single submitter	clinical testing	The c.308_310delTCT variant (also known as p.F103del) is located in coding exon 2 of the RAD51C gene. This variant results from an in-frame TCT deletion at nucleotide positions 308 to 310. This results in the in-frame deletion of a phenylalanine at codon 103. This alteration has been reported in 1 of 1053 hereditary breast cancer families and was not seen in 427 controls (Thompson ER et al. Hum. Mutat., 2012 Jan;33:95-9). The deleted amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000698641	SCV000827321	uncertain significance	Fanconi anemia complementation group O	2023-02-23	criteria provided, single submitter	clinical testing	This variant, c.308_310del, results in the deletion of 1 amino acid(s) of the RAD51C protein (p.Phe103del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with a personal and/or family history of breast cancer (PMID: 21990120). ClinVar contains an entry for this variant (Variation ID: 420040). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Color Diagnostics, LLC DBA Color Health	RCV000569826	SCV001350137	uncertain significance	Hereditary cancer-predisposing syndrome	2019-09-18	criteria provided, single submitter	clinical testing	This variant causes an in-frame deletion of 1 amino acid of the RAD51C protein. Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has been reported in one breast cancer family (PMID: 21990120). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Leiden Open Variation Database	RCV000480944	SCV001365253	uncertain significance	not provided	2011-08-25	no assertion criteria provided	curation	Curator: Arleen D. Auerbach. Submitter to LOVD: Ian Campbell.