rs1060502952
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_002878.4(RAD51D):c.739G>T(p.Val247Leu) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000684 in 1,461,218 control chromosomes in the GnomAD database, with no homozygous occurrence. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V247A) has been classified as Uncertain significance.
Frequency
Consequence
NM_002878.4 missense, splice_region
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51D | NM_002878.4 | c.739G>T | p.Val247Leu | missense_variant, splice_region_variant | 9/10 | ENST00000345365.11 | |
RAD51L3-RFFL | NR_037714.1 | n.491G>T | splice_region_variant, non_coding_transcript_exon_variant | 5/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51D | ENST00000345365.11 | c.739G>T | p.Val247Leu | missense_variant, splice_region_variant | 9/10 | 1 | NM_002878.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461218Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 726912
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 24, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 10, 2023 | The p.V247L variant (also known as c.739G>T) is located in coding exon 9 of the RAD51D gene. The valine at codon 247 is replaced by leucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 9. This alteration has been identified in high-risk non-BRCA1/2 family (Li J et al. J. Med. Genet., 2016 Jan;53:34-42). This amino acid position is highly conserved in available vertebrate species. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at