12-949522-A-C

Position:

• chr12-949522-A-C

Variant summary

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

The NM_134424.4(RAD52):​c.-19+80T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 152,188 control chromosomes in the GnomAD database, including 18,516 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 0.49 (18471 hom., cov: 31)
  • Exomes 𝑓: 0.51 (45 hom.)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.529 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD52	NM_134424.4	c.-19+80T>G		intron_variant		ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.-19+80T>G		intron_variant		1	NM_134424.4	ENSP00000351284	P2

Frequencies

GnomAD3 genomes AF: 0.492 AC: 74578 AN: 151732 Hom.: 18465 Cov.: 31

Gnomad AFR AF: 0.457

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.435

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.534

Gnomad OTH AF: 0.485

GnomAD4 exome AF: 0.515 AC: 174 AN: 338 Hom.: 45 Cov.: 0 AF XY: 0.508 AC XY: 134 AN XY: 264

Gnomad4 AFR exome AF: 0.500

Gnomad4 ASJ exome AF: 1.00

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.522

Gnomad4 OTH exome AF: 0.333

GnomAD4 genome AF: 0.491 AC: 74619 AN: 151850 Hom.: 18471 Cov.: 31 AF XY: 0.487 AC XY: 36164 AN XY: 74210

Gnomad4 AFR AF: 0.457

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.344

Gnomad4 SAS AF: 0.475

Gnomad4 FIN AF: 0.435

Gnomad4 NFE AF: 0.534

Gnomad4 OTH AF: 0.486

Alfa AF: 0.522 Hom.: 15105

Bravo AF: 0.494

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.6
DANN	Benign	0.38

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: rs3748522; hg19: chr12-1058688;