GeneBe

rs587782543

Variant names:

Variant summary

Our verdict is Pathogenic. The variant received 10 ACMG points: 10P and 0B. PVS1PM2

The NM_005732.4(RAD50):​c.1722delA​(p.Lys574AsnfsTer24) 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. Synonymous variant affecting the same amino acid position (i.e. K574K) has been classified as Likely benign. 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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 8.72

Publications

1 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]
RAD50 Gene-Disease associations (from GenCC):
  • Nijmegen breakage syndrome-like disorder
    Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • familial ovarian cancer
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
  • hereditary breast carcinoma
    Inheritance: 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

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RAD50NM_005732.4 linkc.1722delA p.Lys574AsnfsTer24 frameshift_variant Exon 11 of 25 ENST00000378823.8 NP_005723.2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RAD50ENST00000378823.8 linkc.1722delA p.Lys574AsnfsTer24 frameshift_variant Exon 11 of 25 1 NM_005732.4 ENSP00000368100.4
ENSG00000283782ENST00000638452.2 linkc.1425delA p.Lys475AsnfsTer24 frameshift_variant Exon 13 of 27 5 ENSP00000492349.2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1459680
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
726278
African (AFR)
AF:
0.00
AC:
0
AN:
33396
American (AMR)
AF:
0.00
AC:
0
AN:
44716
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26102
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39562
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86196
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53408
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5754
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1110240
Other (OTH)
AF:
0.00
AC:
0
AN:
60306
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
8.7
Mutation Taster
=0/200
disease causing (fs/PTC)

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.030
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: rs587782543; hg19: chr5-131927649; API