chr12-920765-T-C

Position:

• chr12-920765-T-C

Variant summary

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

The NM_134424.4(RAD52):​c.544-3945A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,104 control chromosomes in the GnomAD database, including 1,668 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 0.14 (1668 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204

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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD52	NM_134424.4	c.544-3945A>G		intron_variant		ENST00000358495.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD52	ENST00000358495.8	c.544-3945A>G		intron_variant		1	NM_134424.4	P2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20534 AN: 151984 Hom.: 1664 Cov.: 32

Gnomad AFR AF: 0.0510

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.157

Gnomad EAS AF: 0.182

Gnomad SAS AF: 0.173

Gnomad FIN AF: 0.270

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.136

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.135 AC: 20546 AN: 152104 Hom.: 1668 Cov.: 32 AF XY: 0.140 AC XY: 10370 AN XY: 74330

Gnomad4 AFR AF: 0.0511

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.157

Gnomad4 EAS AF: 0.182

Gnomad4 SAS AF: 0.174

Gnomad4 FIN AF: 0.270

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.136

Alfa AF: 0.142 Hom.: 199

Bravo AF: 0.121

Asia WGS AF: 0.160 AC: 557 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs9634161; hg19: chr12-1029931;