17-35101290-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_002878.4(RAD51D):​c.814C>A​(p.Pro272Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Consequence

RAD51D
NM_002878.4 missense

Scores

8
4
6

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.21
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 3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.829

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RAD51DNM_002878.4 linkuse as main transcriptc.814C>A p.Pro272Thr missense_variant 9/10 ENST00000345365.11 NP_002869.3
RAD51L3-RFFLNR_037714.1 linkuse as main transcriptn.566C>A non_coding_transcript_exon_variant 5/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RAD51DENST00000345365.11 linkuse as main transcriptc.814C>A p.Pro272Thr missense_variant 9/101 NM_002878.4 ENSP00000338790 P1O75771-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.80
BayesDel_addAF
Pathogenic
0.19
D
BayesDel_noAF
Uncertain
0.040
CADD
Pathogenic
28
DANN
Benign
0.97
DEOGEN2
Benign
0.35
.;.;.;T;T;.;.;.
Eigen
Pathogenic
0.76
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
D;D;D;.;D;D;D;D
M_CAP
Benign
0.054
D
MetaRNN
Pathogenic
0.83
D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
1.8
.;.;.;L;L;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D
PROVEAN
Pathogenic
-7.6
.;.;.;D;.;.;.;.
REVEL
Uncertain
0.41
Sift
Pathogenic
0.0
.;.;.;D;.;.;.;.
Sift4G
Uncertain
0.031
D;D;D;D;D;T;D;T
Polyphen
1.0
.;.;.;D;D;D;.;.
Vest4
0.90
MutPred
0.53
.;.;.;Gain of MoRF binding (P = 0.0476);Gain of MoRF binding (P = 0.0476);.;.;.;
MVP
0.80
MPC
0.44
ClinPred
1.0
D
GERP RS
4.9
Varity_R
0.93
gMVP
0.74

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
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: chr17-33428309; API