3-51663313-C-T
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_015106.4(RAD54L2):c.4297C>T(p.Arg1433Trp) variant causes a missense change. The variant allele was found at a frequency of 0.000295 in 1,613,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00030 ( 0 hom. )
Consequence
RAD54L2
NM_015106.4 missense
NM_015106.4 missense
Scores
1
9
9
Clinical Significance
Conservation
PhyloP100: 4.46
Genes affected
RAD54L2 (HGNC:29123): (RAD54 like 2) Predicted to enable ATP hydrolysis activity; protein kinase binding activity; and transcription coregulator activity. Predicted to be involved in DNA duplex unwinding. Predicted to act upstream of or within positive regulation of transcription by RNA polymerase II. Predicted to be located in nuclear speck. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]
TEX264 (HGNC:30247): (testis expressed 264, ER-phagy receptor) Enables signaling receptor activity. Involved in protein-DNA covalent cross-linking repair. Acts upstream of or within reticulophagy. Located in several cellular components, including autophagosome membrane; endoplasmic reticulum membrane; and replication fork. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.24385285).
BS2
High AC in GnomAd4 at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RAD54L2 | NM_015106.4 | c.4297C>T | p.Arg1433Trp | missense_variant | 23/23 | ENST00000684192.1 | NP_055921.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RAD54L2 | ENST00000684192.1 | c.4297C>T | p.Arg1433Trp | missense_variant | 23/23 | NM_015106.4 | ENSP00000507587 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000223 AC: 34AN: 152134Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000183 AC: 46AN: 251124Hom.: 0 AF XY: 0.000177 AC XY: 24AN XY: 135718
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GnomAD4 exome AF: 0.000302 AC: 442AN: 1461704Hom.: 0 Cov.: 32 AF XY: 0.000294 AC XY: 214AN XY: 727132
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152134Hom.: 0 Cov.: 31 AF XY: 0.000148 AC XY: 11AN XY: 74318
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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 | Feb 15, 2023 | The c.4297C>T (p.R1433W) alteration is located in exon 22 (coding exon 21) of the RAD54L2 gene. This alteration results from a C to T substitution at nucleotide position 4297, causing the arginine (R) at amino acid position 1433 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
T
GERP RS
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