rs1555567197
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1_StrongPM2PP5_Very_Strong
The NM_002878.4(RAD51D):c.741_742insTG(p.Thr248Ter) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,358 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Synonymous variant affecting the same amino acid position (i.e. V247V) has been classified as Likely benign.
Frequency
Consequence
NM_002878.4 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 14 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51D | NM_002878.4 | c.741_742insTG | p.Thr248Ter | frameshift_variant | 9/10 | ENST00000345365.11 | |
RAD51L3-RFFL | NR_037714.1 | n.493_494insTG | non_coding_transcript_exon_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51D | ENST00000345365.11 | c.741_742insTG | p.Thr248Ter | frameshift_variant | 9/10 | 1 | NM_002878.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461358Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726946
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Breast-ovarian cancer, familial, susceptibility to, 4 Pathogenic:2
Likely pathogenic, criteria provided, single submitter | clinical testing | Counsyl | Dec 12, 2017 | - - |
Pathogenic, criteria provided, single submitter | clinical testing | Myriad Genetics, Inc. | Apr 06, 2023 | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. - |
Hereditary cancer-predisposing syndrome Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 04, 2023 | The c.740_741dupTG pathogenic mutation, located in coding exon 9 of the RAD51D gene, results from a duplication of TG at nucleotide position 740, causing a translational frameshift with a predicted alternate stop codon (p.T248*). This variant has been identified in an individual diagnosed with an ovarian cancer of endometrioid histology (Song H et al. J. Clin. Oncol., 2015 Sep;33:2901-7). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at