rs2522414

chr5-132576155-G-C

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.365+227G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 152,016 control chromosomes in the GnomAD database, including 9,427 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (9427 hom., cov: 32)
• Consequence: RAD50 NM_005732.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0460

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 5-132576155-G-C is Benign according to our data. Variant chr5-132576155-G-C is described in ClinVar as [Benign]. Clinvar id is 1177683.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.568 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD50	NM_005732.4	c.365+227G>C		intron_variant		ENST00000378823.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD50	ENST00000378823.8	c.365+227G>C		intron_variant		1	NM_005732.4	P1

Frequencies

GnomAD3 genomes AF: 0.312 AC: 47338 AN: 151898 Hom.: 9389 Cov.: 32

Gnomad AFR AF: 0.573

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.233

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.214

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.312 AC: 47426 AN: 152016 Hom.: 9427 Cov.: 32 AF XY: 0.309 AC XY: 22994 AN XY: 74302

Gnomad4 AFR AF: 0.574

Gnomad4 AMR AF: 0.200

Gnomad4 ASJ AF: 0.233

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.214

Gnomad4 OTH AF: 0.269

Alfa AF: 0.289 Hom.: 917

Bravo AF: 0.320

Asia WGS AF: 0.228 AC: 796 AN: 3478

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

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	6.0
Dann	Benign	0.71

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: rs2522414; hg19: chr5-131911847;