dbSNP rs4987208: RAD52:p.Tyr415* (chr12-913403-A-C) – ACMG Classification: Benign (-16 pts)

Variant summary

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

The NM_134424.4(RAD52):c.1245T>G(p.Tyr415*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,607,040 control chromosomes in the GnomAD database, including 866 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 117 hom., cov: 32)

Exomes 𝑓: 0.021 ( 749 hom. )

Consequence

RAD52
NM_134424.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.678

Publications

29 publications found

Variant links:

Genes affected

RAD52 (HGNC:9824): (RAD52 homolog, DNA repair protein) The protein encoded by this gene shares similarity with Saccharomyces cerevisiae Rad52, a protein important for DNA double-strand break repair and homologous recombination. This gene product was shown to bind single-stranded DNA ends, and mediate the DNA-DNA interaction necessary for the annealing of complementary DNA strands. It was also found to interact with DNA recombination protein RAD51, which suggested its role in RAD51 related DNA recombination and repair. A pseudogene of this gene is present on chromosome 2. Alternative splicing results in multiple transcript variants. Additional alternatively spliced transcript variants of this gene have been described, but their full-length nature is not known. [provided by RefSeq, Jul 2014]

RAD52 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 12-913403-A-C is Benign according to our data. Variant chr12-913403-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 403360.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4 link	c.1245T>G	p.Tyr415*	stop_gained	Exon 12 of 12	ENST00000358495.8	NP_602296.2	P43351-1Q5DR82

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8 link	c.1245T>G	p.Tyr415*	stop_gained	Exon 12 of 12	1	NM_134424.4	ENSP00000351284.3		P43351-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3322

AN:

152238

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0976

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0215

GnomAD2 exomes

AF:

0.0353

AC:

8771

AN:

248588

AF XY:

0.0313

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0519

Gnomad EAS exome

AF:

0.000167

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0208

AC:

30250

AN:

1454684

Hom.:

749

Cov.:

AF XY:

0.0203

AC XY:

14711

AN XY:

724152

show subpopulations

African (AFR)

AF:

0.00312

AC:

104

AN:

33300

American (AMR)

AF:

0.143

AC:

6371

AN:

44592

Ashkenazi Jewish (ASJ)

AF:

0.0526

AC:

1370

AN:

26070

East Asian (EAS)

AF:

0.000151

AC:

AN:

39648

South Asian (SAS)

AF:

0.0210

AC:

1803

AN:

86060

European-Finnish (FIN)

AF:

0.0146

AC:

779

AN:

53404

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0166

AC:

18385

AN:

1105680

Other (OTH)

AF:

0.0225

AC:

1354

AN:

60176

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.462

Heterozygous variant carriers

1257

2513

3770

5026

6283

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

766

1532

2298

3064

3830

<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:

0.0219

AC:

3334

AN:

152356

Hom.:

117

Cov.:

AF XY:

0.0228

AC XY:

1698

AN XY:

74496

show subpopulations

African (AFR)

AF:

0.00402

AC:

167

AN:

41580

American (AMR)

AF:

0.0981

AC:

1501

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0545

AC:

189

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.0155

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0140

AC:

149

AN:

10626

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0173

AC:

1175

AN:

68038

Other (OTH)

AF:

0.0217

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

150

300

450

600

750

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

102

136

170

<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:

0.0212

Hom.:

Bravo

AF:

0.0281

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00540

AC:

ESP6500EA

AF:

0.0190

AC:

156

ExAC

AF:

0.0294

AC:

3554

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0156

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency I 1000Genomes: 39/2178= 1.7% -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Pathogenic

0.39

CADD

Pathogenic

(source)

DANN

Benign

0.96

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.051

PhyloP100

0.68

Vest4

0.55

GERP RS

1.8

Mutation Taster

=126/74

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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