12-913513-A-G

Position:

• chr12-913513-A-G

Variant summary

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

The NM_134424.4(RAD52):​c.1196-61T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 1,193,692 control chromosomes in the GnomAD database, including 91,118 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 0.36 (10268 hom., cov: 31)
  • Exomes 𝑓: 0.39 (80850 hom.)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.873

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=-0.62).
• 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	UniProt
RAD52	NM_134424.4	c.1196-61T>C		intron_variant		ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.1196-61T>C		intron_variant		1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.359 AC: 54542 AN: 151896 Hom.: 10259 Cov.: 31

Gnomad AFR AF: 0.264

Gnomad AMI AF: 0.399

Gnomad AMR AF: 0.452

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.328

Gnomad FIN AF: 0.371

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.332

GnomAD4 exome AF: 0.387 AC: 403276 AN: 1041678 Hom.: 80850 AF XY: 0.384 AC XY: 205917 AN XY: 536632

Gnomad4 AFR exome AF: 0.258

Gnomad4 AMR exome AF: 0.518

Gnomad4 ASJ exome AF: 0.302

Gnomad4 EAS exome AF: 0.515

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.389

Gnomad4 OTH exome AF: 0.376

GnomAD4 genome AF: 0.359 AC: 54575 AN: 152014 Hom.: 10268 Cov.: 31 AF XY: 0.360 AC XY: 26775 AN XY: 74282

Gnomad4 AFR AF: 0.264

Gnomad4 AMR AF: 0.453

Gnomad4 ASJ AF: 0.301

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.371

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.330

Alfa AF: 0.374 Hom.: 6535

Bravo AF: 0.363

Asia WGS AF: 0.396 AC: 1378 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.62
CADD	Benign	8.7
DANN	Benign	0.84

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: rs6413436; hg19: chr12-1022679; COSMIC: COSV57273808; COSMIC: COSV57273808;