rs1051672

chr12-912391-G-Achr12-912391-G-C

Variant summary

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

The NM_134424.4(RAD52):c.*1000C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 201,732 control chromosomes in the GnomAD database, including 9,014 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 0.30 (7213 hom., cov: 31)
  • Exomes 𝑓: 0.27 (1801 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.531

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.412 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.*1000C>T		3_prime_UTR_variant	12/12	ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.*1000C>T		3_prime_UTR_variant	12/12	1	NM_134424.4	P2
RAD52	ENST00000228345.9	n.2590C>T		non_coding_transcript_exon_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.297 AC: 45063 AN: 151820 Hom.: 7205 Cov.: 31

Gnomad AFR AF: 0.417

Gnomad AMI AF: 0.133

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.193

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.307

GnomAD4 exome AF: 0.267 AC: 13303 AN: 49794 Hom.: 1801 Cov.: 0 AF XY: 0.270 AC XY: 6250 AN XY: 23118

Gnomad4 AFR exome AF: 0.408

Gnomad4 AMR exome AF: 0.238

Gnomad4 ASJ exome AF: 0.309

Gnomad4 EAS exome AF: 0.220

Gnomad4 SAS exome AF: 0.309

Gnomad4 FIN exome AF: 0.265

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.263

GnomAD4 genome AF: 0.297 AC: 45110 AN: 151938 Hom.: 7213 Cov.: 31 AF XY: 0.294 AC XY: 21828 AN XY: 74222

Gnomad4 AFR AF: 0.417

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.312

Alfa AF: 0.269 Hom.: 2154

Bravo AF: 0.305

Asia WGS AF: 0.293 AC: 1020 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.98
Dann	Benign	0.54

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: rs1051672; hg19: chr12-1021557;