chr12-934668-T-C

Variant names:

• chr12-934668-T-C
• rs10849594
• NM_134424.4:c.-18-1592A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RAD52	NM_134424.4	c.-18-1592A>G		intron_variant	Intron 1 of 11	ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.-18-1592A>G		intron_variant	Intron 1 of 11	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

African (AFR) AF: 0.143 AC: 5951 AN: 41488

American (AMR) AF: 0.123 AC: 1880 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3468

East Asian (EAS) AF: 0.111 AC: 576 AN: 5178

South Asian (SAS) AF: 0.226 AC: 1088 AN: 4810

European-Finnish (FIN) AF: 0.240 AC: 2534 AN: 10556

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.187 AC: 12681 AN: 67990

Other (OTH) AF: 0.164 AC: 345 AN: 2110

Alfa AF: 0.183 Hom.: 508

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
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10849594; hg19: chr12-1043834;