chr1-46261278-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003579.4(RAD54L):c.784C>T(p.Arg262Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,612,590 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R262H) has been classified as Uncertain significance.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000013 ( 0 hom. )
Consequence
RAD54L
NM_003579.4 missense
NM_003579.4 missense
Scores
2
8
4
Clinical Significance
Conservation
PhyloP100: 3.90
Genes affected
RAD54L (HGNC:9826): (RAD54 like) The protein encoded by this gene belongs to the DEAD-like helicase superfamily, and shares similarity with Saccharomyces cerevisiae Rad54, a protein known to be involved in the homologous recombination and repair of DNA. This protein has been shown to play a role in homologous recombination related repair of DNA double-strand breaks. The binding of this protein to double-strand DNA induces a DNA topological change, which is thought to facilitate homologous DNA paring, and stimulate DNA recombination. Alternative splicing results in multiple transcript variants encoding the same protein.[provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RAD54L | NM_003579.4 | c.784C>T | p.Arg262Cys | missense_variant | 8/18 | ENST00000371975.9 | |
RAD54L | NM_001142548.2 | c.784C>T | p.Arg262Cys | missense_variant | 9/19 | ||
RAD54L | NM_001370766.1 | c.244C>T | p.Arg82Cys | missense_variant | 8/18 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RAD54L | ENST00000371975.9 | c.784C>T | p.Arg262Cys | missense_variant | 8/18 | 1 | NM_003579.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000133 AC: 2AN: 150922Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251464Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135908
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GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461668Hom.: 0 Cov.: 36 AF XY: 0.0000110 AC XY: 8AN XY: 727154
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GnomAD4 genome ? AF: 0.0000133 AC: 2AN: 150922Hom.: 0 Cov.: 31 AF XY: 0.0000272 AC XY: 2AN XY: 73590
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 21, 2023 | The p.R262C variant (also known as c.784C>T), located in coding exon 8 of the RAD54L gene, results from a C to T substitution at nucleotide position 784. The arginine at codon 262 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D
PrimateAI
Benign
T
Sift4G
Uncertain
D;T;T
Polyphen
0.98
.;D;D
Vest4
0.67, 0.67
MutPred
0.61
.;Loss of disorder (P = 0.0268);Loss of disorder (P = 0.0268);
MVP
MPC
0.44
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at