5-132565805-T-G

Variant names:

• chr5-132565805-T-G
• rs2299015
• NM_005732.4:c.213+6438T>G

Variant summary

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

The NM_005732.4(RAD50):​c.213+6438T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.193 in 152,116 control chromosomes in the GnomAD database, including 2,958 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 0.19 (2958 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.373
• Publications: 10 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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 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.213+6438T>G		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.213+6438T>G		intron	N/A	ENSP00000368100.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.-85+6438T>G		intron	N/A	ENSP00000492349.2
	RAD50	ENST00000416135.5	TSL:1	c.-85+6438T>G		intron	N/A	ENSP00000389515.1

Frequencies

GnomAD3 genomes AF: 0.193 AC: 29342 AN: 151998 Hom.: 2951 Cov.: 31

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.151

Gnomad ASJ AF: 0.225

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.197

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.193 AC: 29374 AN: 152116 Hom.: 2958 Cov.: 31 AF XY: 0.194 AC XY: 14400 AN XY: 74352

African (AFR) AF: 0.159 AC: 6588 AN: 41512

American (AMR) AF: 0.151 AC: 2301 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.225 AC: 780 AN: 3468

East Asian (EAS) AF: 0.177 AC: 919 AN: 5180

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4820

European-Finnish (FIN) AF: 0.242 AC: 2559 AN: 10564

Middle Eastern (MID) AF: 0.199 AC: 58 AN: 292

European-Non Finnish (NFE) AF: 0.214 AC: 14570 AN: 67980

Other (OTH) AF: 0.190 AC: 400 AN: 2110

Alfa AF: 0.131 Hom.: 295

Bravo AF: 0.182

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.1
DANN	Benign	0.74
PhyloP100		-0.37
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: rs2299015; hg19: chr5-131901497;