rs786202750
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 16P and 4B. PVS1PP5_Very_StrongBS2
The NM_002878.4(RAD51D):βc.564delβ(p.Val189TrpfsTer5) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,724 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (β β ). Synonymous variant affecting the same amino acid position (i.e. T188T) has been classified as Uncertain significance. Variant results in nonsense mediated mRNA decay.
Frequency
Consequence
NM_002878.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51D | NM_002878.4 | c.564del | p.Val189TrpfsTer5 | frameshift_variant | 6/10 | ENST00000345365.11 | |
RAD51L3-RFFL | NR_037714.1 | n.316del | non_coding_transcript_exon_variant | 2/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51D | ENST00000345365.11 | c.564del | p.Val189TrpfsTer5 | frameshift_variant | 6/10 | 1 | NM_002878.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460724Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2AN XY: 726534
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 30, 2024 | The c.564delT pathogenic mutation, located in coding exon 6 of the RAD51D gene, results from a deletion of one nucleotide at nucleotide position 564, causing a translational frameshift with a predicted alternate stop codon (p.V189Tfs*5). This alteration has been reported in a patient with high-grade serous epithelial ovarian cancer at age 54 (Song H et al. J. Clin. Oncol., 2015 Sep;33:2901-7). It has also been reported in an individual with triple negative breast cancer at age 39; however, this individual was also noted to have a mutation in the PALB2 gene (Couch FJ et al. J. Clin. Oncol., 2015 Feb;33:304-11). In another study, this variant was reported in 3/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. - |
Breast-ovarian cancer, familial, susceptibility to, 4 Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Jan 04, 2024 | This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at