rs370212314
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_058216.3(RAD51C):c.335G>A(p.Gly112Glu) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,944 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. G112A) has been classified as Likely benign.
Frequency
Consequence
NM_058216.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51C | NM_058216.3 | c.335G>A | p.Gly112Glu | missense_variant | 2/9 | ENST00000337432.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51C | ENST00000337432.9 | c.335G>A | p.Gly112Glu | missense_variant | 2/9 | 1 | NM_058216.3 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251296Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135830
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461844Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 727218
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152100Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74288
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 07, 2022 | The p.G112E variant (also known as c.335G>A), located in coding exon 2 of the RAD51C gene, results from a G to A substitution at nucleotide position 335. The glycine at codon 112 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Fanconi anemia complementation group O Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 01, 2023 | This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 112 of the RAD51C protein (p.Gly112Glu). 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. 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. ClinVar contains an entry for this variant (Variation ID: 661813). This variant has not been reported in the literature in individuals affected with RAD51C-related conditions. This variant is not present in population databases (gnomAD no frequency). - |
Breast-ovarian cancer, familial, susceptibility to, 3 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 11, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at