17-58692695-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_058216.3(RAD51C):c.52C>T(p.Pro18Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000279 in 1,614,220 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P18L) has been classified as Uncertain significance.
Frequency
Consequence
NM_058216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51C | NM_058216.3 | c.52C>T | p.Pro18Ser | missense_variant | 1/9 | ENST00000337432.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51C | ENST00000337432.9 | c.52C>T | p.Pro18Ser | missense_variant | 1/9 | 1 | NM_058216.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251454Hom.: 0 AF XY: 0.0000736 AC XY: 10AN XY: 135918
GnomAD4 exome AF: 0.0000301 AC: 44AN: 1461890Hom.: 1 Cov.: 32 AF XY: 0.0000385 AC XY: 28AN XY: 727246
GnomAD4 genome ? AF: 0.00000656 AC: 1AN: 152330Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74482
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 07, 2023 | This missense variant replaces proline with serine at codon 18 of the RAD51C protein. Computational prediction suggests that this variant may not impact protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two individuals affected with breast and/or ovarian cancer (PMID: 29470806). This variant has been identified in 10/251454 chromosomes 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 06, 2023 | The p.P18S variant (also known as c.52C>T), located in coding exon 1 of the RAD51C gene, results from a C to T substitution at nucleotide position 52. The proline at codon 18 is replaced by serine, an amino acid with similar properties. This variant was observed in a study of 1010 unrelated Indian patients with breast and/or ovarian cancer (Singh J et al. Breast Cancer Res Treat, 2018 Jul;170:189-196). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Feb 05, 2018 | This variant is denoted RAD51C c.52C>T at the cDNA level, p.Pro18Ser (P18S) at the protein level, and results in the change of a Proline to a Serine (CCG>TCG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. RAD51C Pro18Ser was not observed at a significant allele frequency in large population cohorts (Lek 2016). RAD51C Pro18Ser is located in the region required for holiday junction resolution activity (UniProt). In-silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether RAD51C Pro18Ser is a pathogenic or benign variant. We consider it to be a variant of uncertain significance. - |
Fanconi anemia complementation group O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 16, 2023 | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 18 of the RAD51C protein (p.Pro18Ser). This variant is present in population databases (rs547142453, gnomAD 0.03%). This missense change has been observed in individual(s) with a personal and/or family history of breast and/or ovarian cancer (PMID: 29470806). ClinVar contains an entry for this variant (Variation ID: 232581). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt RAD51C 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at