Genetic Variant RAD52:c.-19+30G>C (chr12-949572-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_134424.4(RAD52):c.-19+30G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 152,440 control chromosomes in the GnomAD database, including 1,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1220 hom., cov: 32)

Exomes 𝑓: 0.094 ( 2 hom. )

Consequence

RAD52
NM_134424.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.103

Publications

7 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:

ENSG00000299067 (HGNC:):

ENSG00000299067 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.77).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4 link	c.-19+30G>C		intron_variant	Intron 1 of 11	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.-19+30G>C		intron_variant	Intron 1 of 11	1	NM_134424.4	ENSP00000351284.3		P43351-1

Frequencies

GnomAD3 genomes

AF:

0.122

AC:

18541

AN:

151928

Hom.:

1222

Cov.:

show subpopulations

Gnomad AFR

AF:

0.143

Gnomad AMI

AF:

0.0714

Gnomad AMR

AF:

0.0754

Gnomad ASJ

AF:

0.121

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.165

Gnomad FIN

AF:

0.227

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.103

Gnomad OTH

AF:

0.104

GnomAD4 exome

AF:

0.0939

AC:

AN:

394

Hom.:

Cov.:

AF XY:

0.0845

AC XY:

AN XY:

296

show subpopulations

African (AFR)

AF:

0.250

AC:

AN:

American (AMR)

AF:

0.00

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.167

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0853

AC:

AN:

340

Other (OTH)

AF:

0.125

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.469

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.122

AC:

18557

AN:

152046

Hom.:

1220

Cov.:

AF XY:

0.126

AC XY:

9388

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.143

AC:

5927

AN:

41470

American (AMR)

AF:

0.0752

AC:

1150

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.121

AC:

420

AN:

3468

East Asian (EAS)

AF:

0.111

AC:

574

AN:

5164

South Asian (SAS)

AF:

0.165

AC:

793

AN:

4816

European-Finnish (FIN)

AF:

0.227

AC:

2399

AN:

10560

Middle Eastern (MID)

AF:

0.133

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.103

AC:

6971

AN:

67972

Other (OTH)

AF:

0.104

AC:

219

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

794

1588

2382

3176

3970

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

222

444

666

888

1110

<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:

0.119

Hom.:

150

Bravo

AF:

0.111

Asia WGS

AF:

0.160

AC:

557

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

CADD

Benign

3.2

(source)

DANN

Benign

0.82

PhyloP100

-0.10

PromoterAI

-0.053

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over