rs1051669

Positions:

• chr12-913286-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134424.4(RAD52):​c.*105G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.241 in 853,418 control chromosomes in the GnomAD database, including 25,554 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 0.25 (4855 hom., cov: 32)
  • Exomes 𝑓: 0.24 (20699 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.*105G>A		3_prime_UTR_variant	12/12	ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.*105G>A		3_prime_UTR_variant	12/12	1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37994 AN: 151936 Hom.: 4850 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.239 AC: 167374 AN: 701364 Hom.: 20699 Cov.: 9 AF XY: 0.240 AC XY: 88683 AN XY: 369420

Gnomad4 AFR exome AF: 0.281

Gnomad4 AMR exome AF: 0.223

Gnomad4 ASJ exome AF: 0.299

Gnomad4 EAS exome AF: 0.211

Gnomad4 SAS exome AF: 0.257

Gnomad4 FIN exome AF: 0.194

Gnomad4 NFE exome AF: 0.239

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.250 AC: 38032 AN: 152054 Hom.: 4855 Cov.: 32 AF XY: 0.247 AC XY: 18392 AN XY: 74338

Gnomad4 AFR AF: 0.280

Gnomad4 AMR AF: 0.229

Gnomad4 ASJ AF: 0.312

Gnomad4 EAS AF: 0.192

Gnomad4 SAS AF: 0.271

Gnomad4 FIN AF: 0.187

Gnomad4 NFE AF: 0.247

Gnomad4 OTH AF: 0.274

Alfa AF: 0.252 Hom.: 4745

Bravo AF: 0.254

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.68

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

Other links and lift over

dbSNP: rs1051669; hg19: chr12-1022452;