chr5-132595759-TAA-T
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2
The NM_005732.4(RAD50):c.2164_2165delAA(p.Lys722GlyfsTer5) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
RAD50
NM_005732.4 frameshift
NM_005732.4 frameshift
Scores
Not classified
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 9.32
Publications
0 publications found
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]
RAD50 Gene-Disease associations (from GenCC):
- Nijmegen breakage syndrome-like disorderInheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
- familial ovarian cancerInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
- hereditary breast carcinomaInheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 10 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Ensembl
| Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
|---|---|---|---|---|---|---|---|---|---|---|
| RAD50 | ENST00000378823.8 | c.2164_2165delAA | p.Lys722GlyfsTer5 | frameshift_variant | Exon 13 of 25 | 1 | NM_005732.4 | ENSP00000368100.4 | ||
| ENSG00000283782 | ENST00000638452.2 | c.1867_1868delAA | p.Lys623GlyfsTer5 | frameshift_variant | Exon 15 of 27 | 5 | ENSP00000492349.2 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1448568Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 720822
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1448568
Hom.:
AF XY:
AC XY:
0
AN XY:
720822
African (AFR)
AF:
AC:
0
AN:
33104
American (AMR)
AF:
AC:
0
AN:
44366
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25740
East Asian (EAS)
AF:
AC:
0
AN:
39058
South Asian (SAS)
AF:
AC:
0
AN:
85840
European-Finnish (FIN)
AF:
AC:
0
AN:
52304
Middle Eastern (MID)
AF:
AC:
0
AN:
5704
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1102806
Other (OTH)
AF:
AC:
0
AN:
59646
GnomAD4 genome
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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