rs2244012

Positions:

• chr5-132565533-A-G
• chr5-132565533-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.213+6166A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 151,798 control chromosomes in the GnomAD database, including 10,354 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 0.32 (10354 hom., cov: 31)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.800

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=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.213+6166A>G		intron_variant		ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.213+6166A>G		intron_variant		1	NM_005732.4	P1

Frequencies

GnomAD3 genomes AF: 0.324 AC: 49188 AN: 151680 Hom.: 10315 Cov.: 31

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.236

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.219

Gnomad OTH AF: 0.279

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

GnomAD4 genome AF: 0.325 AC: 49275 AN: 151798 Hom.: 10354 Cov.: 31 AF XY: 0.322 AC XY: 23880 AN XY: 74168

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.203

Gnomad4 ASJ AF: 0.236

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.237

Gnomad4 FIN AF: 0.244

Gnomad4 NFE AF: 0.219

Gnomad4 OTH AF: 0.276

Alfa AF: 0.226 Hom.: 9656

Bravo AF: 0.333

Asia WGS AF: 0.229 AC: 798 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.60
DANN	Benign	0.52

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: rs2244012; hg19: chr5-131901225;