rs200018296
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BS2_Supporting
The NM_002878.4(RAD51D):āc.250A>Gā(p.Thr84Ala) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,613,722 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T84I) has been classified 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 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD51D | NM_002878.4 | c.250A>G | p.Thr84Ala | missense_variant | 3/10 | ENST00000345365.11 | |
RAD51L3-RFFL | NR_037714.1 | n.232+2777A>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD51D | ENST00000345365.11 | c.250A>G | p.Thr84Ala | missense_variant | 3/10 | 1 | NM_002878.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152096Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251472Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135918
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461508Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727080
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74416
ClinVar
Submissions by phenotype
Hereditary cancer-predisposing syndrome Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 22, 2021 | The p.T84A variant (also known as c.250A>G), located in coding exon 3 of the RAD51D gene, results from an A to G substitution at nucleotide position 250. The threonine at codon 84 is replaced by alanine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Apr 03, 2019 | - - |
Breast-ovarian cancer, familial, susceptibility to, 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2023 | 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 expected to disrupt RAD51D protein function. ClinVar contains an entry for this variant (Variation ID: 185051). This missense change has been observed in individual(s) with breast cancer (PMID: 35039564). This variant is present in population databases (rs200018296, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 84 of the RAD51D protein (p.Thr84Ala). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at