Variant chr12-914052-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_134424.4(RAD52):c.1037C>A(p.Ser346Ter) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.013 in 1,614,122 control chromosomes in the GnomAD database, including 251 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.011 ( 19 hom., cov: 32)

Exomes 𝑓: 0.013 ( 232 hom. )

Consequence

RAD52
NM_134424.4 stop_gained

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.103

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 made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP6

Variant 12-914052-G-T is Benign according to our data. Variant chr12-914052-G-T is described in ClinVar as [Benign]. Clinvar id is 3037321.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0106 (1621/152236) while in subpopulation SAS AF= 0.0545 (263/4826). AF 95% confidence interval is 0.0491. There are 19 homozygotes in gnomad4. There are 889 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4 linkuse as main transcript	c.1037C>A	p.Ser346Ter	stop_gained	11/12	ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8 linkuse as main transcript	c.1037C>A	p.Ser346Ter	stop_gained	11/12	1	NM_134424.4	P2	P43351-1

Frequencies

GnomAD3 genomes

AF:

0.0107

AC:

1624

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00239

Gnomad AMI

AF:

0.00877

Gnomad AMR

AF:

0.00674

Gnomad ASJ

AF:

0.0326

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.0545

Gnomad FIN

AF:

0.0136

Gnomad MID

AF:

0.0601

Gnomad NFE

AF:

0.0110

Gnomad OTH

AF:

0.0119

GnomAD3 exomes

AF:

0.0165

AC:

4118

AN:

249554

Hom.:

AF XY:

0.0189

AC XY:

2557

AN XY:

135402

show subpopulations

Gnomad AFR exome

AF:

0.00142

Gnomad AMR exome

AF:

0.00455

Gnomad ASJ exome

AF:

0.0330

Gnomad EAS exome

AF:

0.0215

Gnomad SAS exome

AF:

0.0481

Gnomad FIN exome

AF:

0.0150

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.0157

GnomAD4 exome

AF:

0.0132

AC:

19292

AN:

1461886

Hom.:

232

Cov.:

AF XY:

0.0145

AC XY:

10529

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00203

Gnomad4 AMR exome

AF:

0.00532

Gnomad4 ASJ exome

AF:

0.0336

Gnomad4 EAS exome

AF:

0.0131

Gnomad4 SAS exome

AF:

0.0467

Gnomad4 FIN exome

AF:

0.0139

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.0172

GnomAD4 genome

AF:

0.0106

AC:

1621

AN:

152236

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

889

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00236

Gnomad4 AMR

AF:

0.00673

Gnomad4 ASJ

AF:

0.0326

Gnomad4 EAS

AF:

0.0195

Gnomad4 SAS

AF:

0.0545

Gnomad4 FIN

AF:

0.0136

Gnomad4 NFE

AF:

0.0110

Gnomad4 OTH

AF:

0.0128

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.00894

TwinsUK

AF:

0.0111

AC:

ALSPAC

AF:

0.00856

AC:

ESP6500AA

AF:

0.00305

AC:

ESP6500EA

AF:

0.0130

AC:

108

ExAC

AF:

0.0168

AC:

2032

Asia WGS

AF:

0.0400

AC:

137

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

RAD52-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 14, 2021

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Pathogenic

0.14

CADD

Uncertain

DANN

Benign

0.79

Eigen

Benign

-0.31

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.084

MutationTaster

Benign

1.0

A;A;A

Vest4

0.86

GERP RS

-2.1

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over