12-926876-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000545564.5(RAD52):c.538G>A(p.Gly180Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0315 in 1,536,408 control chromosomes in the GnomAD database, including 849 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.021 ( 50 hom., cov: 32)

Exomes 𝑓: 0.033 ( 799 hom. )

Consequence

RAD52
ENST00000545564.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.296

Publications

13 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003516376).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.0215 (3270/152186) while in subpopulation NFE AF = 0.0343 (2334/68000). AF 95% confidence interval is 0.0332. There are 50 homozygotes in GnomAd4. There are 1490 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 50 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000545564.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RAD52	NM_134424.4	MANE Select	c.467+269G>A		intron	N/A	NP_602296.2
RAD52	NM_001297420.1		c.538G>A	p.Gly180Arg	missense	Exon 6 of 7	NP_001284349.1
RAD52	NR_123713.2		n.780G>A		non_coding_transcript_exon	Exon 8 of 14

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
RAD52	ENST00000545564.5	TSL:1	c.538G>A	p.Gly180Arg	missense	Exon 6 of 7	ENSP00000440268.1
RAD52	ENST00000461568.5	TSL:1	n.*173G>A		non_coding_transcript_exon	Exon 7 of 12	ENSP00000436008.1
RAD52	ENST00000543912.5	TSL:1	n.*51G>A		non_coding_transcript_exon	Exon 5 of 10	ENSP00000439583.1

Frequencies

GnomAD3 genomes

AF:

0.0215

AC:

3272

AN:

152068

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00616

Gnomad AMI

AF:

0.0143

Gnomad AMR

AF:

0.0268

Gnomad ASJ

AF:

0.0216

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.00207

Gnomad FIN

AF:

0.0109

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0343

Gnomad OTH

AF:

0.0258

GnomAD2 exomes

AF:

0.0219

AC:

3119

AN:

142260

AF XY:

0.0219

show subpopulations

Gnomad AFR exome

AF:

0.00614

Gnomad AMR exome

AF:

0.0187

Gnomad ASJ exome

AF:

0.0236

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0110

Gnomad NFE exome

AF:

0.0376

Gnomad OTH exome

AF:

0.0261

GnomAD4 exome

AF:

0.0326

AC:

45103

AN:

1384222

Hom.:

799

Cov.:

AF XY:

0.0318

AC XY:

21710

AN XY:

683104

show subpopulations

African (AFR)

AF:

0.00618

AC:

195

AN:

31578

American (AMR)

AF:

0.0192

AC:

687

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0247

AC:

623

AN:

25178

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35728

South Asian (SAS)

AF:

0.00433

AC:

343

AN:

79222

European-Finnish (FIN)

AF:

0.0113

AC:

394

AN:

35000

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

5538

European-Non Finnish (NFE)

AF:

0.0383

AC:

41275

AN:

1078400

Other (OTH)

AF:

0.0260

AC:

1507

AN:

57878

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

2248

4497

6745

8994

11242

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1572

3144

4716

6288

7860

<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:

0.0215

AC:

3270

AN:

152186

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1490

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.00614

AC:

255

AN:

41542

American (AMR)

AF:

0.0268

AC:

409

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3468

East Asian (EAS)

AF:

0.000386

AC:

AN:

5188

South Asian (SAS)

AF:

0.00187

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0109

AC:

115

AN:

10578

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0343

AC:

2334

AN:

68000

Other (OTH)

AF:

0.0256

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

158

316

475

633

791

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

114

152

190

<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:

0.0259

Hom.:

Bravo

AF:

0.0230

TwinsUK

AF:

0.0402

AC:

149

ALSPAC

AF:

0.0350

AC:

135

ESP6500AA

AF:

0.00730

AC:

ESP6500EA

AF:

0.0321

AC:

204

ExAC

AF:

0.00789

AC:

479

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.16

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.2

(source)

DANN

Benign

0.52

Eigen

Benign

-0.86

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.36

MetaRNN

Benign

0.0035

MetaSVM

Benign

-1.1

PhyloP100

0.30

PROVEAN

Benign

1.5

REVEL

Benign

0.090

Sift

Benign

0.036

Sift4G

Benign

0.87

Vest4

0.18

MutPred

0.60

Loss of catalytic residue at G180 (P = 0.0242)

ClinPred

0.0051

GERP RS

-2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over