rs1555567518

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_002878.4(RAD51D):​c.699G>C​(p.Glu233Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. 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. E233G) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)

Consequence

RAD51D
NM_002878.4 missense

Scores

3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.730
Variant links:
Genes affected
RAD51D (HGNC:9823): (RAD51 paralog D) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, which are known to be involved in the homologous recombination and repair of DNA. This protein forms a complex with several other members of the RAD51 family, including RAD51L1, RAD51L2, and XRCC2. The protein complex formed with this protein has been shown to catalyze homologous pairing between single- and double-stranded DNA, and is thought to play a role in the early stage of recombinational repair of DNA. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream ring finger and FYVE-like domain containing 1 (RFFL) gene. [provided by RefSeq, Jan 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.33086005).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAD51DNM_002878.4 linkuse as main transcriptc.699G>C p.Glu233Asp missense_variant 8/10 ENST00000345365.11 NP_002869.3
RAD51L3-RFFLNR_037714.1 linkuse as main transcriptn.451G>C non_coding_transcript_exon_variant 4/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAD51DENST00000345365.11 linkuse as main transcriptc.699G>C p.Glu233Asp missense_variant 8/101 NM_002878.4 ENSP00000338790 P1O75771-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 14, 2024The p.E233D variant (also known as c.699G>C), located in coding exon 8 of the RAD51D gene, results from a G to C substitution at nucleotide position 699. The glutamic acid at codon 233 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.41
BayesDel_addAF
Uncertain
0.037
T
BayesDel_noAF
Benign
-0.18
CADD
Benign
21
DANN
Benign
0.93
DEOGEN2
Benign
0.15
.;.;.;T;T;.;.;.;.;T
Eigen
Benign
0.013
Eigen_PC
Benign
0.074
FATHMM_MKL
Benign
0.70
D
LIST_S2
Uncertain
0.91
D;D;D;.;D;D;D;D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Benign
0.33
T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
0.82
.;.;.;L;L;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PROVEAN
Benign
-1.5
.;.;.;N;.;.;.;.;.;.
REVEL
Benign
0.10
Sift
Benign
0.38
.;.;.;T;.;.;.;.;.;.
Sift4G
Benign
0.20
T;T;T;T;T;T;T;T;T;.
Polyphen
0.62, 1.0
.;.;.;P;P;D;.;.;.;.
Vest4
0.24
MutPred
0.39
.;.;.;Gain of MoRF binding (P = 0.1108);Gain of MoRF binding (P = 0.1108);.;.;.;.;.;
MVP
0.84
MPC
0.32
ClinPred
0.90
D
GERP RS
3.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.34
gMVP
0.63

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-33430312; API