rs4987207

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

The NM_134424.4(RAD52):c.1037C>A(p.Ser346*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,614,122 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.011 ( 19 hom., cov: 32)

Exomes 𝑓: 0.013 ( 232 hom. )

Consequence

RAD52
NM_134424.4 stop_gained

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.103

Publications

37 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:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 12-914052-G-T is Benign according to our data. Variant chr12-914052-G-T is described in ClinVar as Benign. ClinVar VariationId is 3037321.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.0106 (1621/152236) while in subpopulation SAS AF = 0.0545 (263/4826). AF 95% confidence interval is 0.0491. There are 19 homozygotes in GnomAd4. There are 889 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 19 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD52	NM_134424.4	MANE Select	c.1037C>A	p.Ser346*	stop_gained	Exon 11 of 12	NP_602296.2	Q5DR82
RAD52	NM_001297419.1		c.1037C>A	p.Ser346*	stop_gained	Exon 11 of 12	NP_001284348.1	Q5DR82
RAD52	NM_001297421.2		c.806C>A	p.Ser269*	stop_gained	Exon 9 of 10	NP_001284350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD52	ENST00000358495.8	TSL:1 MANE Select	c.1037C>A	p.Ser346*	stop_gained	Exon 11 of 12	ENSP00000351284.3	P43351-1
RAD52	ENST00000430095.6	TSL:1	c.1037C>A	p.Ser346*	stop_gained	Exon 11 of 12	ENSP00000387901.2	P43351-1
RAD52	ENST00000461568.5	TSL:1	n.*875C>A		non_coding_transcript_exon	Exon 12 of 12	ENSP00000436008.1	P43351-3

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1624

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.0119

GnomAD2 exomes

AF:

0.0165

AC:

4118

AN:

249554

AF XY:

0.0189

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00455

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.0215

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0132

AC:

19292

AN:

1461886

Hom.:

232

Cov.:

AF XY:

0.0145

AC XY:

10529

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00203

AC:

AN:

33480

American (AMR)

AF:

0.00532

AC:

238

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0336

AC:

879

AN:

26136

East Asian (EAS)

AF:

0.0131

AC:

521

AN:

39700

South Asian (SAS)

AF:

0.0467

AC:

4025

AN:

86258

European-Finnish (FIN)

AF:

0.0139

AC:

743

AN:

53420

Middle Eastern (MID)

AF:

0.0347

AC:

200

AN:

5768

European-Non Finnish (NFE)

AF:

0.0104

AC:

11580

AN:

1112004

Other (OTH)

AF:

0.0172

AC:

1038

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

1183

2366

3549

4732

5915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

478

956

1434

1912

2390

<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:

0.0106

AC:

1621

AN:

152236

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

889

AN XY:

74418

show subpopulations

African (AFR)

AF:

0.00236

AC:

AN:

41524

American (AMR)

AF:

0.00673

AC:

103

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0326

AC:

113

AN:

3470

East Asian (EAS)

AF:

0.0195

AC:

101

AN:

5176

South Asian (SAS)

AF:

0.0545

AC:

263

AN:

4826

European-Finnish (FIN)

AF:

0.0136

AC:

144

AN:

10608

Middle Eastern (MID)

AF:

0.0544

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0110

AC:

748

AN:

68010

Other (OTH)

AF:

0.0128

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

171

256

342

427

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

110

<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:

0.0117

Hom.:

Bravo

AF:

0.00894

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00305

AC:

ESP6500EA

AF:

0.0130

AC:

108

ExAC

AF:

0.0168

AC:

2032

Asia WGS

AF:

0.0400

AC:

137

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Congenital myasthenic syndrome 19 (1)

RAD52-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

(source)

DANN

Benign

0.79

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.084

PhyloP100

0.10

Vest4

0.86

GERP RS

-2.1

Mutation Taster

=134/66

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over