rs11226

Positions:

• chr12-912647-G-A

Variant summary

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

The NM_134424.4(RAD52):​c.*744C>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 0.433 in 171,536 control chromosomes in the GnomAD database, including 16,526 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 0.44 (14326 hom., cov: 24)
  • Exomes 𝑓: 0.42 (2200 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD52	NM_134424.4	c.*744C>T		3_prime_UTR_variant	12/12	ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.*744C>T		3_prime_UTR_variant	12/12	1	NM_134424.4	ENSP00000351284	P2

Frequencies

GnomAD3 genomes AF: 0.436 AC: 64456 AN: 147892 Hom.: 14309 Cov.: 24

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.417 AC: 9817 AN: 23550 Hom.: 2200 Cov.: 0 AF XY: 0.413 AC XY: 4445 AN XY: 10762

Gnomad4 AFR exome AF: 0.357

Gnomad4 AMR exome AF: 0.510

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.480

Gnomad4 SAS exome AF: 0.321

Gnomad4 FIN exome AF: 0.286

Gnomad4 NFE exome AF: 0.403

Gnomad4 OTH exome AF: 0.406

GnomAD4 genome AF: 0.436 AC: 64497 AN: 147986 Hom.: 14326 Cov.: 24 AF XY: 0.437 AC XY: 31382 AN XY: 71852

Gnomad4 AFR AF: 0.376

Gnomad4 AMR AF: 0.519

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.333

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.453

Gnomad4 OTH AF: 0.414

Alfa AF: 0.448 Hom.: 1943

Bravo AF: 0.441

Asia WGS AF: 0.410 AC: 1425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.69

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: rs11226; hg19: chr12-1021813;