rs2301713

Variant names:

• chr5-132616304-T-C
• rs2301713
• NM_005732.4:c.3164+174T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000378823.8(RAD50):​c.3164+174T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 152,120 control chromosomes in the GnomAD database, including 4,196 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.23 (4196 hom., cov: 32)
• Consequence: RAD50 ENST00000378823.8 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.989
• Publications: 22 publications found

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]

RAD50 Gene-Disease associations (from GenCC):

• Nijmegen breakage syndrome-like disorder

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• familial ovarian cancer

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ENSG00000283782 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 5-132616304-T-C is Benign according to our data. Variant chr5-132616304-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182998.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000378823.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	NM_005732.4	MANE Select	c.3164+174T>C		intron	N/A	NP_005723.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD50	ENST00000378823.8	TSL:1 MANE Select	c.3164+174T>C		intron	N/A	ENSP00000368100.4
	ENSG00000283782	ENST00000638452.2	TSL:5	c.2867+174T>C		intron	N/A	ENSP00000492349.2
	RAD50	ENST00000533482.5	TSL:1	n.*2790+174T>C		intron	N/A	ENSP00000431225.1

Frequencies

GnomAD3 genomes AF: 0.230 AC: 34931 AN: 152002 Hom.: 4192 Cov.: 32

Gnomad AFR AF: 0.282

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.235

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.244

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.216

Gnomad OTH AF: 0.215

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

GnomAD4 genome AF: 0.230 AC: 34949 AN: 152120 Hom.: 4196 Cov.: 32 AF XY: 0.231 AC XY: 17163 AN XY: 74374

African (AFR) AF: 0.282 AC: 11677 AN: 41474

American (AMR) AF: 0.165 AC: 2525 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.235 AC: 814 AN: 3470

East Asian (EAS) AF: 0.178 AC: 920 AN: 5178

South Asian (SAS) AF: 0.225 AC: 1087 AN: 4828

European-Finnish (FIN) AF: 0.244 AC: 2582 AN: 10594

Middle Eastern (MID) AF: 0.260 AC: 76 AN: 292

European-Non Finnish (NFE) AF: 0.216 AC: 14707 AN: 67970

Other (OTH) AF: 0.213 AC: 450 AN: 2114

Alfa AF: 0.215 Hom.: 4666

Bravo AF: 0.223

Asia WGS AF: 0.199 AC: 695 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	9.6
DANN	Benign	0.58
PhyloP100		0.99
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2301713; hg19: chr5-131951996;