rs10849594

Positions:

• chr12-934668-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.-18-1592A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.17 in 152,076 control chromosomes in the GnomAD database, including 2,218 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 0.17 (2218 hom., cov: 31)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.240

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]

LOC124902855 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD52	NM_134424.4	c.-18-1592A>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.-18-1592A>G		intron_variant		1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25811 AN: 151958 Hom.: 2219 Cov.: 31

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.180

Gnomad AMR AF: 0.123

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.226

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.165

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

GnomAD4 genome AF: 0.170 AC: 25829 AN: 152076 Hom.: 2218 Cov.: 31 AF XY: 0.171 AC XY: 12694 AN XY: 74332

Gnomad4 AFR AF: 0.143

Gnomad4 AMR AF: 0.123

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.226

Gnomad4 FIN AF: 0.240

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.164

Alfa AF: 0.184 Hom.: 500

Bravo AF: 0.159

Asia WGS AF: 0.178 AC: 620 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	12
DANN	Benign	0.42

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: rs10849594; hg19: chr12-1043834;