rs2706347

Positions:

• chr5-132569425-G-T

Variant summary

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

The NM_005732.4(RAD50):​c.214-6352G>T 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 151,950 control chromosomes in the GnomAD database, including 9,350 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 (9350 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.342

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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.214-6352G>T		intron_variant		ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.214-6352G>T		intron_variant		1	NM_005732.4	P1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47184 AN: 151832 Hom.: 9312 Cov.: 32

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.199

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.271

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

GnomAD4 genome AF: 0.311 AC: 47272 AN: 151950 Hom.: 9350 Cov.: 32 AF XY: 0.308 AC XY: 22902 AN XY: 74264

Gnomad4 AFR AF: 0.572

Gnomad4 AMR AF: 0.199

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.268

Alfa AF: 0.307 Hom.: 1622

Bravo AF: 0.319

Asia WGS AF: 0.227 AC: 791 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.25
DANN	Benign	0.48

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

Publications

LitVar

Other links and lift over

dbSNP: rs2706347; hg19: chr5-131905117;