17-35101322-T-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_002878.4(RAD51D):c.782A>C(p.Lys261Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,850 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_002878.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD51D | ENST00000345365.11 | c.782A>C | p.Lys261Thr | missense_variant | Exon 9 of 10 | 1 | NM_002878.4 | ENSP00000338790.6 | ||
ENSG00000267618 | ENST00000593039.5 | c.305A>C | p.Lys102Thr | missense_variant | Exon 5 of 7 | 2 | ENSP00000466834.1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251406Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135880
GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461850Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727222
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not provided Uncertain:2
- -
- -
Hereditary cancer-predisposing syndrome Uncertain:1
The p.K261T variant (also known as c.782A>C), located in coding exon 9 of the RAD51D gene, results from an A to C substitution at nucleotide position 782. The lysine at codon 261 is replaced by threonine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. 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. -
Breast-ovarian cancer, familial, susceptibility to, 4 Uncertain:1
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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 410569). This variant has not been reported in the literature in individuals affected with RAD51D-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 261 of the RAD51D protein (p.Lys261Thr). -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at