Genetic Variant NM_134424.4:c.1196-61T>C (chr12-913513-A-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.1196-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,193,692 control chromosomes in the GnomAD database, including 91,118 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 0.36 ( 10268 hom., cov: 31)

Exomes 𝑓: 0.39 ( 80850 hom. )

Consequence

RAD52
NM_134424.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.873

Publications

21 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4 link	c.1196-61T>C		intron_variant	Intron 11 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.1196-61T>C		intron_variant	Intron 11 of 11	1	NM_134424.4	ENSP00000351284.3		P43351-1

Frequencies

GnomAD3 genomes

AF:

0.359

AC:

54542

AN:

151896

Hom.:

10259

Cov.:

show subpopulations

Gnomad AFR

AF:

0.264

Gnomad AMI

AF:

0.399

Gnomad AMR

AF:

0.452

Gnomad ASJ

AF:

0.301

Gnomad EAS

AF:

0.531

Gnomad SAS

AF:

0.328

Gnomad FIN

AF:

0.371

Gnomad MID

AF:

0.231

Gnomad NFE

AF:

0.387

Gnomad OTH

AF:

0.332

GnomAD4 exome

AF:

0.387

AC:

403276

AN:

1041678

Hom.:

80850

AF XY:

0.384

AC XY:

205917

AN XY:

536632

show subpopulations

African (AFR)

AF:

0.258

AC:

6308

AN:

24410

American (AMR)

AF:

0.518

AC:

20502

AN:

39580

Ashkenazi Jewish (ASJ)

AF:

0.302

AC:

6848

AN:

22638

East Asian (EAS)

AF:

0.515

AC:

19489

AN:

37820

South Asian (SAS)

AF:

0.328

AC:

24647

AN:

75074

European-Finnish (FIN)

AF:

0.377

AC:

18643

AN:

49400

Middle Eastern (MID)

AF:

0.218

AC:

1059

AN:

4854

European-Non Finnish (NFE)

AF:

0.389

AC:

288286

AN:

741344

Other (OTH)

AF:

0.376

AC:

17494

AN:

46558

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

12524

25048

37571

50095

62619

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7434

14868

22302

29736

37170

<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:

0.359

AC:

54575

AN:

152014

Hom.:

10268

Cov.:

AF XY:

0.360

AC XY:

26775

AN XY:

74282

show subpopulations

African (AFR)

AF:

0.264

AC:

10941

AN:

41466

American (AMR)

AF:

0.453

AC:

6920

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.301

AC:

1043

AN:

3468

East Asian (EAS)

AF:

0.531

AC:

2739

AN:

5160

South Asian (SAS)

AF:

0.327

AC:

1575

AN:

4818

European-Finnish (FIN)

AF:

0.371

AC:

3912

AN:

10534

Middle Eastern (MID)

AF:

0.231

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.387

AC:

26317

AN:

67980

Other (OTH)

AF:

0.330

AC:

696

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1738

3477

5215

6954

8692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

526

1052

1578

2104

2630

<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:

0.377

Hom.:

9437

Bravo

AF:

0.363

Asia WGS

AF:

0.396

AC:

1378

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

8.7

(source)

DANN

Benign

0.84

PhyloP100

-0.87

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over