rs2706377

Positions:

• chr5-132603805-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005732.4(RAD50):​c.2398-115A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0182 in 1,045,102 control chromosomes in the GnomAD database, including 1,783 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.069 (1124 hom., cov: 32)
  • Exomes 𝑓: 0.0095 (659 hom.)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.158

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]

ENSG00000283782 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 5-132603805-A-G is Benign according to our data. Variant chr5-132603805-A-G is described in ClinVar as [Benign]. Clinvar id is 1242868.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD50	NM_005732.4	c.2398-115A>G		intron_variant		ENST00000378823.8	NP_005723.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8	c.2398-115A>G		intron_variant		1	NM_005732.4	ENSP00000368100.4
ENSG00000283782	ENST00000640655.2	c.2101-115A>G		intron_variant		5		ENSP00000491596.2

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10447 AN: 152166 Hom.: 1121 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0281

Gnomad ASJ AF: 0.00259

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0120

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.00338

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.00954 AC: 8516 AN: 892818 Hom.: 659 AF XY: 0.00890 AC XY: 4047 AN XY: 454852

Gnomad4 AFR exome AF: 0.239

Gnomad4 AMR exome AF: 0.0190

Gnomad4 ASJ exome AF: 0.00123

Gnomad4 EAS exome AF: 0.0000909

Gnomad4 SAS exome AF: 0.00854

Gnomad4 FIN exome AF: 0.000134

Gnomad4 NFE exome AF: 0.00279

Gnomad4 OTH exome AF: 0.0194

GnomAD4 genome AF: 0.0687 AC: 10469 AN: 152284 Hom.: 1124 Cov.: 32 AF XY: 0.0666 AC XY: 4957 AN XY: 74480

Gnomad4 AFR AF: 0.232

Gnomad4 AMR AF: 0.0281

Gnomad4 ASJ AF: 0.00259

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0120

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00337

Gnomad4 OTH AF: 0.0510

Alfa AF: 0.0417 Hom.: 84

Bravo AF: 0.0802

Asia WGS AF: 0.0180 AC: 64 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	12
DANN	Benign	0.66

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: rs2706377; hg19: chr5-131939497;