GeneBe

rs786201205

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_005732.4(RAD50):​c.3769T>A​(p.Ser1257Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1257A) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

RAD50
NM_005732.4 missense

Scores

2
4
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.85

Publications

0 publications found
Variant links:
Genes affected
RAD50 (HGNC:9816): (RAD50 double strand break repair protein) The protein encoded by this gene is highly similar to Saccharomyces cerevisiae Rad50, a protein involved in DNA double-strand break repair. This protein forms a complex with MRE11 and NBS1. The protein complex binds to DNA and displays numerous enzymatic activities that are required for nonhomologous joining of DNA ends. This protein, cooperating with its partners, is important for DNA double-strand break repair, cell cycle checkpoint activation, telomere maintenance, and meiotic recombination. Knockout studies of the mouse homolog suggest this gene is essential for cell growth and viability. Mutations in this gene are the cause of Nijmegen breakage syndrome-like disorder.[provided by RefSeq, Apr 2010]
TH2LCRR (HGNC:40495): (T helper type 2 locus control region associated RNA)

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34893054).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005732.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RAD50
NM_005732.4
MANE Select
c.3769T>Ap.Ser1257Thr
missense
Exon 25 of 25NP_005723.2
TH2LCRR
NR_132125.1
n.189+4A>T
splice_region intron
N/A
TH2LCRR
NR_132126.1
n.175-3929A>T
intron
N/A

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
RAD50
ENST00000378823.8
TSL:1 MANE Select
c.3769T>Ap.Ser1257Thr
missense
Exon 25 of 25ENSP00000368100.4
ENSG00000283782
ENST00000638452.2
TSL:5
c.3472T>Ap.Ser1158Thr
missense
Exon 27 of 27ENSP00000492349.2
RAD50
ENST00000533482.5
TSL:1
n.*3395T>A
non_coding_transcript_exon
Exon 25 of 25ENSP00000431225.1

Frequencies

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

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Uncertain
0.025
T
BayesDel_noAF
Benign
-0.20
CADD
Uncertain
24
DANN
Uncertain
0.99
DEOGEN2
Benign
0.16
T
Eigen
Uncertain
0.35
Eigen_PC
Uncertain
0.43
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.83
T
M_CAP
Benign
0.0054
T
MetaRNN
Benign
0.35
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.9
L
PhyloP100
5.9
PrimateAI
Pathogenic
0.85
D
REVEL
Benign
0.11
Sift4G
Benign
0.33
T
Polyphen
0.76
P
Vest4
0.12
MutPred
0.39
Loss of disorder (P = 0.0693)
MVP
0.67
ClinPred
0.91
D
GERP RS
5.6
Varity_R
0.36
gMVP
0.58
Mutation Taster
=76/24
polymorphism

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

Other links and lift over

dbSNP: rs786201205; hg19: chr5-131977886; API