rs2299014

Variant names:

• chr5-132567707-A-C
• rs2299014
• NM_005732.4:c.214-8070A>C

Your query was ambiguous. Multiple possible variants found:

• chr5-132567707-A-C
• chr5-132567707-A-G
• chr5-132567707-A-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.214-8070A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 152,074 control chromosomes in the GnomAD database, including 9,362 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 0.31 (9362 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.27
• Publications: 9 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD50	NM_005732.4	c.214-8070A>C		intron_variant	Intron 2 of 24	ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.214-8070A>C		intron_variant	Intron 2 of 24	1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000638452.2	c.-84-8070A>C		intron_variant	Intron 4 of 26	5		ENSP00000492349.2

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47366 AN: 151956 Hom.: 9364 Cov.: 31

Gnomad AFR AF: 0.0893

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.329

Gnomad ASJ AF: 0.403

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.333

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.312

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

GnomAD4 genome AF: 0.311 AC: 47363 AN: 152074 Hom.: 9362 Cov.: 31 AF XY: 0.306 AC XY: 22760 AN XY: 74338

African (AFR) AF: 0.0890 AC: 3695 AN: 41508

American (AMR) AF: 0.329 AC: 5028 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.403 AC: 1398 AN: 3470

East Asian (EAS) AF: 0.0650 AC: 336 AN: 5172

South Asian (SAS) AF: 0.385 AC: 1857 AN: 4826

European-Finnish (FIN) AF: 0.333 AC: 3518 AN: 10550

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30456 AN: 67944

Other (OTH) AF: 0.309 AC: 651 AN: 2108

Alfa AF: 0.292 Hom.: 3170

Bravo AF: 0.295

Asia WGS AF: 0.227 AC: 789 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.35
PhyloP100		1.3
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: rs2299014; hg19: chr5-131903399;