rs2706372

Variant names:

• chr5-132599785-C-T
• rs2706372
• NM_005732.4:c.2208-3515C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):​c.2208-3515C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.326 in 151,684 control chromosomes in the GnomAD database, including 10,604 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.33 (10604 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.292
• Publications: 17 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 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

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.615 is higher than 0.05.

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	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	NM_005732.4	MANE Select	c.2208-3515C>T		intron	N/A	NP_005723.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.2208-3515C>T		intron	N/A	ENSP00000368100.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.1911-3515C>T		intron	N/A	ENSP00000492349.2
	RAD50	ENST00000533482.5	TSL:1	n.*1834-3515C>T		intron	N/A	ENSP00000431225.1

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49328 AN: 151566 Hom.: 10560 Cov.: 31

Gnomad AFR AF: 0.621

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.233

Gnomad MID AF: 0.261

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.280

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.326 AC: 49420 AN: 151684 Hom.: 10604 Cov.: 31 AF XY: 0.323 AC XY: 23938 AN XY: 74110

African (AFR) AF: 0.621 AC: 25670 AN: 41314

American (AMR) AF: 0.204 AC: 3109 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.241 AC: 834 AN: 3466

East Asian (EAS) AF: 0.177 AC: 908 AN: 5140

South Asian (SAS) AF: 0.236 AC: 1135 AN: 4802

European-Finnish (FIN) AF: 0.233 AC: 2446 AN: 10506

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14548 AN: 67902

Other (OTH) AF: 0.277 AC: 582 AN: 2102

Alfa AF: 0.346 Hom.: 1687

Bravo AF: 0.337

Asia WGS AF: 0.227 AC: 793 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.9
DANN	Benign	0.63
PhyloP100		0.29
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2706372; hg19: chr5-131935477;