Genetic Variant NM_134424.4:c.-19+80T>G (chr12-949522-A-C) – 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+80T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,188 control chromosomes in the GnomAD database, including 18,516 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 0.49 ( 18471 hom., cov: 31)

Exomes 𝑓: 0.51 ( 45 hom. )

Consequence

RAD52
NM_134424.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.645

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:

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=-0.84).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4 link	c.-19+80T>G		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+80T>G		intron_variant	Intron 1 of 11	1	NM_134424.4	ENSP00000351284.3		P43351-1

Frequencies

GnomAD3 genomes

AF:

0.492

AC:

74578

AN:

151732

Hom.:

18465

Cov.:

show subpopulations

Gnomad AFR

AF:

0.457

Gnomad AMI

AF:

0.428

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.427

Gnomad EAS

AF:

0.344

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.435

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.534

Gnomad OTH

AF:

0.485

GnomAD4 exome

AF:

0.515

AC:

174

AN:

338

Hom.:

Cov.:

AF XY:

0.508

AC XY:

134

AN XY:

264

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

1.00

AC:

AN:

East Asian (EAS)

AF:

0.429

AC:

AN:

South Asian (SAS)

AF:

0.500

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AF:

0.750

AC:

AN:

European-Non Finnish (NFE)

AF:

0.522

AC:

145

AN:

278

Other (OTH)

AF:

0.333

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.491

AC:

74619

AN:

151850

Hom.:

18471

Cov.:

AF XY:

0.487

AC XY:

36164

AN XY:

74210

show subpopulations

African (AFR)

AF:

0.457

AC:

18918

AN:

41402

American (AMR)

AF:

0.511

AC:

7806

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.427

AC:

1482

AN:

3472

East Asian (EAS)

AF:

0.344

AC:

1768

AN:

5146

South Asian (SAS)

AF:

0.475

AC:

2285

AN:

4806

European-Finnish (FIN)

AF:

0.435

AC:

4575

AN:

10526

Middle Eastern (MID)

AF:

0.442

AC:

130

AN:

294

European-Non Finnish (NFE)

AF:

0.534

AC:

36244

AN:

67928

Other (OTH)

AF:

0.486

AC:

1021

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

1973

3946

5918

7891

9864

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

674

1348

2022

2696

3370

<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:

0.519

Hom.:

19286

Bravo

AF:

0.494

Asia WGS

AF:

0.415

AC:

1445

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.6

(source)

DANN

Benign

0.38

PhyloP100

-0.65

PromoterAI

-0.11

Neutral

(source)

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