5-132609272-CTT-CTTT

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_005732.4(RAD50):c.2923-5dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.015 in 1,609,978 control chromosomes in the GnomAD database, including 2,235 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.069 ( 1126 hom., cov: 31)

Exomes 𝑓: 0.0094 ( 1109 hom. )

Consequence

RAD50
NM_005732.4 splice_region, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: 1.01

Publications

3 publications found

Variant links:

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

RAD50 links:

ENSG00000283782 (HGNC:):

ENSG00000283782 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP6

Variant 5-132609272-C-CT is Benign according to our data. Variant chr5-132609272-C-CT is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 140787.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
RAD50	NM_005732.4 link	c.2923-5dupT		splice_region_variant, intron_variant	Intron 18 of 24	ENST00000378823.8	NP_005723.2	Q92878-1A5D6Y3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD50	ENST00000378823.8 link	c.2923-11_2923-10insT		intron_variant	Intron 18 of 24	1	NM_005732.4	ENSP00000368100.4		Q92878-1
ENSG00000283782	ENST00000638452.2 link	c.2626-11_2626-10insT		intron_variant	Intron 20 of 26	5		ENSP00000492349.2		A0A1W2PQ90

Frequencies

GnomAD3 genomes

AF:

0.0687

AC:

10440

AN:

151954

Hom.:

1123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.232

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0281

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.00337

Gnomad OTH

AF:

0.0513

GnomAD2 exomes

AF:

0.0199

AC:

4902

AN:

246788

AF XY:

0.0158

show subpopulations

Gnomad AFR exome

AF:

0.239

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.00232

Gnomad EAS exome

AF:

0.000165

Gnomad FIN exome

AF:

0.000139

Gnomad NFE exome

AF:

0.00330

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00937

AC:

13661

AN:

1457906

Hom.:

1109

Cov.:

AF XY:

0.00863

AC XY:

6256

AN XY:

725028

show subpopulations

African (AFR)

AF:

0.242

AC:

8032

AN:

33160

American (AMR)

AF:

0.0166

AC:

733

AN:

44230

Ashkenazi Jewish (ASJ)

AF:

0.00138

AC:

AN:

26038

East Asian (EAS)

AF:

0.000126

AC:

AN:

39552

South Asian (SAS)

AF:

0.00816

AC:

692

AN:

84802

European-Finnish (FIN)

AF:

0.000150

AC:

AN:

53302

Middle Eastern (MID)

AF:

0.0301

AC:

173

AN:

5746

European-Non Finnish (NFE)

AF:

0.00260

AC:

2883

AN:

1110856

Other (OTH)

AF:

0.0182

AC:

1099

AN:

60220

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

629

1257

1886

2514

3143

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

288

576

864

1152

1440

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0688

AC:

10462

AN:

152072

Hom.:

1126

Cov.:

AF XY:

0.0666

AC XY:

4953

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.232

AC:

9621

AN:

41464

American (AMR)

AF:

0.0281

AC:

429

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00259

AC:

AN:

3470

East Asian (EAS)

AF:

0.000193

AC:

AN:

5182

South Asian (SAS)

AF:

0.0116

AC:

AN:

4810

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10582

Middle Eastern (MID)

AF:

0.0374

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00335

AC:

228

AN:

67970

Other (OTH)

AF:

0.0508

AC:

107

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

409

819

1228

1638

2047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0320

Hom.:

Bravo

AF:

0.0801

Asia WGS

AF:

0.0190

AC:

AN:

3474

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary cancer-predisposing syndrome

Benign:4

Jun 30, 2015

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 08, 2013

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 30, 2012

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 24, 2016

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: The RAD50 c.2923-5dupT variant involves the insertion of a nucleotide in the intronic region. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 2771/115606 control chromosomes (257 homozygotes) at a frequency of 0.0239693, which is approximately 383 times the estimated maximal expected allele frequency of a pathogenic RAD50 variant (0.0000625), suggesting this variant is a benign polymorphism. In addition, another clinical diagnostic laboratory classified this variant as likely benign, without evidence to independently evaluate. Taken together, this variant is classified as benign. -

not specified

Benign:1

Mar 16, 2021

Quest Diagnostics Nichols Institute San Juan Capistrano

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over