chr12-914296-C-A

Position:

• chr12-914296-C-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_134424.4(RAD52):​c.967+135G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,370,988 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (20 hom.)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.732

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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAdExome4 at 20 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.967+135G>T		intron_variant		ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.967+135G>T		intron_variant		1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 482 AN: 152140 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00546 AC: 6659 AN: 1218730 Hom.: 20 Cov.: 18 AF XY: 0.00538 AC XY: 3246 AN XY: 603334

Gnomad4 AFR exome AF: 0.000779

Gnomad4 AMR exome AF: 0.00510

Gnomad4 ASJ exome AF: 0.00310

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00185

Gnomad4 FIN exome AF: 0.000556

Gnomad4 NFE exome AF: 0.00629

Gnomad4 OTH exome AF: 0.00564

GnomAD4 genome AF: 0.00317 AC: 482 AN: 152258 Hom.: 1 Cov.: 32 AF XY: 0.00285 AC XY: 212 AN XY: 74444

Gnomad4 AFR AF: 0.000987

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00207

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00497

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.00344 Hom.: 0

Bravo AF: 0.00351

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

not provided, no classification provided

literature only

Harris Lab, University of Minnesota

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.52

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: rs104895068; hg19: chr12-1023462;