Variant 12-913403-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM4BP6_ModerateBA1

The NM_134424.4(RAD52):c.1245T>G(p.Tyr415Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 1,607,040 control chromosomes in the GnomAD database, including 866 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.022 ( 117 hom., cov: 32)

Exomes 𝑓: 0.021 ( 749 hom. )

Consequence

RAD52
NM_134424.4 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.678

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 -8 ACMG points.

PM4

Stoplost variant in NM_134424.4 Downstream stopcodon found after 11 codons.

BP6

Variant 12-913403-A-C is Benign according to our data. Variant chr12-913403-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 403360.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4 linkuse as main transcript	c.1245T>G	p.Tyr415Ter	stop_gained	12/12	ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8 linkuse as main transcript	c.1245T>G	p.Tyr415Ter	stop_gained	12/12	1	NM_134424.4	P2	P43351-1

Frequencies

GnomAD3 genomes

AF:

0.0218

AC:

3322

AN:

152238

Hom.:

115

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00403

Gnomad AMI

AF:

0.0330

Gnomad AMR

AF:

0.0976

Gnomad ASJ

AF:

0.0545

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0153

Gnomad FIN

AF:

0.0140

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.0173

Gnomad OTH

AF:

0.0215

GnomAD3 exomes

AF:

0.0353

AC:

8771

AN:

248588

Hom.:

440

AF XY:

0.0313

AC XY:

4223

AN XY:

135024

show subpopulations

Gnomad AFR exome

AF:

0.00381

Gnomad AMR exome

AF:

0.148

Gnomad ASJ exome

AF:

0.0519

Gnomad EAS exome

AF:

0.000167

Gnomad SAS exome

AF:

0.0212

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.0174

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0208

AC:

30250

AN:

1454684

Hom.:

749

Cov.:

AF XY:

0.0203

AC XY:

14711

AN XY:

724152

show subpopulations

Gnomad4 AFR exome

AF:

0.00312

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.0526

Gnomad4 EAS exome

AF:

0.000151

Gnomad4 SAS exome

AF:

0.0210

Gnomad4 FIN exome

AF:

0.0146

Gnomad4 NFE exome

AF:

0.0166

Gnomad4 OTH exome

AF:

0.0225

GnomAD4 genome

AF:

0.0219

AC:

3334

AN:

152356

Hom.:

117

Cov.:

AF XY:

0.0228

AC XY:

1698

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.00402

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.0545

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0155

Gnomad4 FIN

AF:

0.0140

Gnomad4 NFE

AF:

0.0173

Gnomad4 OTH

AF:

0.0217

Alfa

AF:

0.0205

Hom.:

Bravo

AF:

0.0281

TwinsUK

AF:

0.0143

AC:

ALSPAC

AF:

0.0163

AC:

ESP6500AA

AF:

0.00540

AC:

ESP6500EA

AF:

0.0190

AC:

156

ExAC

AF:

0.0294

AC:

3554

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.0149

EpiControl

AF:

0.0156

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency I 1000Genomes: 39/2178= 1.7% -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Pathogenic

0.39

Cadd

Pathogenic

Dann

Benign

0.96

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.051

MutationTaster

Benign

1.0

D;D;D

Vest4

0.55

GERP RS

1.8

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over