Variant 12-926876-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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. 11/13 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

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 made for transcript

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 50 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4 linkuse as main transcript	c.467+269G>A		intron_variant		ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8 linkuse as main transcript	c.467+269G>A		intron_variant		1	NM_134424.4	P2	P43351-1

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

GnomAD3 exomes

AF:

0.0219

AC:

3119

AN:

142260

Hom.:

AF XY:

0.0219

AC XY:

1655

AN XY:

75510

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 SAS exome

AF:

0.00378

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

Gnomad4 AFR exome

AF:

0.00618

Gnomad4 AMR exome

AF:

0.0192

Gnomad4 ASJ exome

AF:

0.0247

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00433

Gnomad4 FIN exome

AF:

0.0113

Gnomad4 NFE exome

AF:

0.0383

Gnomad4 OTH exome

AF:

0.0260

GnomAD4 genome

AF:

0.0215

AC:

3270

AN:

152186

Hom.:

Cov.:

AF XY:

0.0200

AC XY:

1490

AN XY:

74400

show subpopulations

Gnomad4 AFR

AF:

0.00614

Gnomad4 AMR

AF:

0.0268

Gnomad4 ASJ

AF:

0.0216

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.00187

Gnomad4 FIN

AF:

0.0109

Gnomad4 NFE

AF:

0.0343

Gnomad4 OTH

AF:

0.0256

Alfa

AF:

0.0251

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.65

CADD

Benign

5.2

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

MutationTaster

Benign

1.0

N;N;N;N;N

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

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over