dbSNP rs11571424: RAD52:c.348+131G>A (chr12-929688-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_134424.4(RAD52):c.348+131G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 883,670 control chromosomes in the GnomAD database, including 6,174 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 0.094 ( 789 hom., cov: 32)

Exomes 𝑓: 0.12 ( 5385 hom. )

Consequence

RAD52
NM_134424.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.06

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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.0).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4 link	c.348+131G>A		intron_variant	Intron 5 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.348+131G>A		intron_variant	Intron 5 of 11	1	NM_134424.4	ENSP00000351284.3		P43351-1

Frequencies

GnomAD3 genomes

AF:

0.0938

AC:

14258

AN:

152040

Hom.:

789

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0411

Gnomad AMI

AF:

0.135

Gnomad AMR

AF:

0.0803

Gnomad ASJ

AF:

0.108

Gnomad EAS

AF:

0.0902

Gnomad SAS

AF:

0.149

Gnomad FIN

AF:

0.0923

Gnomad MID

AF:

0.117

Gnomad NFE

AF:

0.124

Gnomad OTH

AF:

0.105

GnomAD3 exomes

AF:

0.106

AC:

26456

AN:

250284

Hom.:

1619

AF XY:

0.112

AC XY:

15183

AN XY:

135362

show subpopulations

Gnomad AFR exome

AF:

0.0396

Gnomad AMR exome

AF:

0.0505

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.0801

Gnomad SAS exome

AF:

0.156

Gnomad FIN exome

AF:

0.0867

Gnomad NFE exome

AF:

0.125

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.116

AC:

84610

AN:

731512

Hom.:

5385

Cov.:

AF XY:

0.119

AC XY:

46782

AN XY:

391778

show subpopulations

Gnomad4 AFR exome

AF:

0.0404

Gnomad4 AMR exome

AF:

0.0543

Gnomad4 ASJ exome

AF:

0.109

Gnomad4 EAS exome

AF:

0.0993

Gnomad4 SAS exome

AF:

0.156

Gnomad4 FIN exome

AF:

0.0919

Gnomad4 NFE exome

AF:

0.123

Gnomad4 OTH exome

AF:

0.109

GnomAD4 genome

AF:

0.0937

AC:

14262

AN:

152158

Hom.:

789

Cov.:

AF XY:

0.0931

AC XY:

6923

AN XY:

74380

show subpopulations

Gnomad4 AFR

AF:

0.0411

Gnomad4 AMR

AF:

0.0802

Gnomad4 ASJ

AF:

0.108

Gnomad4 EAS

AF:

0.0898

Gnomad4 SAS

AF:

0.150

Gnomad4 FIN

AF:

0.0923

Gnomad4 NFE

AF:

0.124

Gnomad4 OTH

AF:

0.103

Alfa

AF:

0.113

Hom.:

462

Bravo

AF:

0.0889

Asia WGS

AF:

0.105

AC:

366

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.022

DANN

Benign

0.48

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