12-913286-C-T

Variant names:

• chr12-913286-C-T
• rs1051669
• NM_134424.4:c.*105G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134424.4(RAD52):​c.*105G>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 0.241 in 853,418 control chromosomes in the GnomAD database, including 25,554 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 0.25 (4855 hom., cov: 32)
  • Exomes 𝑓: 0.24 (20699 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.144
• Publications: 30 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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.276 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_134424.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	NM_134424.4	MANE Select	c.*105G>A		3_prime_UTR	Exon 12 of 12	NP_602296.2	Q5DR82
	RAD52	NM_001297419.1		c.*105G>A		3_prime_UTR	Exon 12 of 12	NP_001284348.1	Q5DR82
	RAD52	NM_001297421.2		c.*105G>A		3_prime_UTR	Exon 10 of 10	NP_001284350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.*105G>A		3_prime_UTR	Exon 12 of 12	ENSP00000351284.3	P43351-1
	RAD52	ENST00000430095.6	TSL:1	c.*105G>A		3_prime_UTR	Exon 12 of 12	ENSP00000387901.2	P43351-1
	RAD52	ENST00000904782.1		c.*105G>A		3_prime_UTR	Exon 12 of 12	ENSP00000574841.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37994 AN: 151936 Hom.: 4850 Cov.: 32

Gnomad AFR AF: 0.280

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.230

Gnomad ASJ AF: 0.312

Gnomad EAS AF: 0.191

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.247

Gnomad OTH AF: 0.268

GnomAD4 exome AF: 0.239 AC: 167374 AN: 701364 Hom.: 20699 Cov.: 9 AF XY: 0.240 AC XY: 88683 AN XY: 369420

African (AFR) AF: 0.281 AC: 4875 AN: 17352

American (AMR) AF: 0.223 AC: 6748 AN: 30300

Ashkenazi Jewish (ASJ) AF: 0.299 AC: 5001 AN: 16706

East Asian (EAS) AF: 0.211 AC: 7540 AN: 35770

South Asian (SAS) AF: 0.257 AC: 14798 AN: 57536

European-Finnish (FIN) AF: 0.194 AC: 9245 AN: 47566

Middle Eastern (MID) AF: 0.332 AC: 1197 AN: 3606

European-Non Finnish (NFE) AF: 0.239 AC: 109575 AN: 457596

Other (OTH) AF: 0.240 AC: 8395 AN: 34932

GnomAD4 genome AF: 0.250 AC: 38032 AN: 152054 Hom.: 4855 Cov.: 32 AF XY: 0.247 AC XY: 18392 AN XY: 74338

African (AFR) AF: 0.280 AC: 11614 AN: 41462

American (AMR) AF: 0.229 AC: 3504 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.312 AC: 1080 AN: 3466

East Asian (EAS) AF: 0.192 AC: 993 AN: 5174

South Asian (SAS) AF: 0.271 AC: 1305 AN: 4812

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10572

Middle Eastern (MID) AF: 0.316 AC: 93 AN: 294

European-Non Finnish (NFE) AF: 0.247 AC: 16767 AN: 67982

Other (OTH) AF: 0.274 AC: 578 AN: 2112

Alfa AF: 0.253 Hom.: 5440

Bravo AF: 0.254

Asia WGS AF: 0.261 AC: 909 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.5
DANN	Benign	0.68
PhyloP100		0.14
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: rs1051669; hg19: chr12-1022452; COSMIC: COSV107206788; COSMIC: COSV107206788;