rs7310449

Positions:

• chr12-912949-G-A
• chr12-912949-G-C
• chr12-912949-G-T

Variant summary

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

The NM_134424.4(RAD52):​c.*442C>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 0.429 in 204,060 control chromosomes in the GnomAD database, including 19,271 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 0.43 (14315 hom., cov: 30)
  • Exomes 𝑓: 0.43 (4956 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.273

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]

RAD52 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• 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.*442C>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	c.*442C>T		3_prime_UTR_variant	12/12	1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.430 AC: 65113 AN: 151576 Hom.: 14297 Cov.: 30

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.514

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.336

Gnomad FIN AF: 0.445

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.450

Gnomad OTH AF: 0.411

GnomAD4 exome AF: 0.429 AC: 22470 AN: 52366 Hom.: 4956 Cov.: 0 AF XY: 0.426 AC XY: 10438 AN XY: 24518

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.512

Gnomad4 ASJ exome AF: 0.398

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.303

Gnomad4 FIN exome AF: 0.333

Gnomad4 NFE exome AF: 0.424

Gnomad4 OTH exome AF: 0.417

GnomAD4 genome AF: 0.430 AC: 65163 AN: 151694 Hom.: 14315 Cov.: 30 AF XY: 0.431 AC XY: 31897 AN XY: 74074

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.515

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.531

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.445

Gnomad4 NFE AF: 0.450

Gnomad4 OTH AF: 0.409

Alfa AF: 0.438 Hom.: 14268

Bravo AF: 0.435

Asia WGS AF: 0.408 AC: 1417 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.62

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: rs7310449; hg19: chr12-1022115;