12-913075-C-T

Variant names:

• chr12-913075-C-T
• rs104895066
• NM_134424.4:c.*316G>A

Variant summary

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

The NM_134424.4(RAD52):​c.*316G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 151,648 control chromosomes in the GnomAD database, including 14,149 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 (14149 hom., cov: 31)
  • Exomes 𝑓: 0.43 (13034 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819

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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4	c.*316G>A		3_prime_UTR_variant	Exon 12 of 12	ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495	c.*316G>A		3_prime_UTR_variant	Exon 12 of 12	1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64708 AN: 151530 Hom.: 14131 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.409

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.433 AC: 58524 AN: 135126 Hom.: 13034 Cov.: 0 AF XY: 0.428 AC XY: 28391 AN XY: 66334

Gnomad4 AFR exome AF: 0.346

Gnomad4 AMR exome AF: 0.520

Gnomad4 ASJ exome AF: 0.408

Gnomad4 EAS exome AF: 0.500

Gnomad4 SAS exome AF: 0.287

Gnomad4 FIN exome AF: 0.421

Gnomad4 NFE exome AF: 0.435

Gnomad4 OTH exome AF: 0.430

GnomAD4 genome AF: 0.427 AC: 64756 AN: 151648 Hom.: 14149 Cov.: 31 AF XY: 0.428 AC XY: 31692 AN XY: 74072

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.513

Gnomad4 ASJ AF: 0.404

Gnomad4 EAS AF: 0.530

Gnomad4 SAS AF: 0.336

Gnomad4 FIN AF: 0.446

Gnomad4 NFE AF: 0.452

Gnomad4 OTH AF: 0.407

Alfa AF: 0.445 Hom.: 1658

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.58

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: rs104895066; hg19: chr12-1022241; COSMIC: COSV57273741; COSMIC: COSV57273741;