rs2706370

Positions:

• chr5-132597324-A-C
• chr5-132597324-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005732.4(RAD50):​c.2207+1514A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,086 control chromosomes in the GnomAD database, including 10,331 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 (10331 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.541

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.593 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4	c.2207+1514A>C		intron_variant		ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.2207+1514A>C		intron_variant		1	NM_005732.4	ENSP00000368100	P1

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49782 AN: 151968 Hom.: 10299 Cov.: 32

Gnomad AFR AF: 0.599

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.208

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.190

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.224

Gnomad OTH AF: 0.281

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

GnomAD4 genome AF: 0.328 AC: 49854 AN: 152086 Hom.: 10331 Cov.: 32 AF XY: 0.326 AC XY: 24220 AN XY: 74342

Gnomad4 AFR AF: 0.599

Gnomad4 AMR AF: 0.208

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.191

Gnomad4 SAS AF: 0.240

Gnomad4 FIN AF: 0.267

Gnomad4 NFE AF: 0.224

Gnomad4 OTH AF: 0.278

Alfa AF: 0.327 Hom.: 1365

Bravo AF: 0.336

Asia WGS AF: 0.230 AC: 803 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.3
DANN	Benign	0.73

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2706370; hg19: chr5-131933016; COSMIC: COSV54756990; COSMIC: COSV54756990;