12-912647-G-A

Variant names:

• chr12-912647-G-A
• rs11226
• NM_134424.4:c.*744C>T

Variant summary

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

The NM_134424.4(RAD52):​c.*744C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 171,536 control chromosomes in the GnomAD database, including 16,526 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 0.44 (14326 hom., cov: 24)
  • Exomes 𝑓: 0.42 (2200 hom.)
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• Publications: 22 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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.514 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	NM_134424.4	MANE Select	c.*744C>T		3_prime_UTR	Exon 12 of 12	NP_602296.2
	RAD52	NR_123713.2		n.2394C>T		non_coding_transcript_exon	Exon 14 of 14
	RAD52	NM_001297419.1		c.*744C>T		3_prime_UTR	Exon 12 of 12	NP_001284348.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.*744C>T		3_prime_UTR	Exon 12 of 12	ENSP00000351284.3
	RAD52	ENST00000430095.6	TSL:1	c.*744C>T		3_prime_UTR	Exon 12 of 12	ENSP00000387901.2
	RAD52	ENST00000228345.9	TSL:2	n.2334C>T		non_coding_transcript_exon	Exon 11 of 11

Frequencies

GnomAD3 genomes AF: 0.436 AC: 64456 AN: 147892 Hom.: 14309 Cov.: 24

Gnomad AFR AF: 0.376

Gnomad AMI AF: 0.528

Gnomad AMR AF: 0.519

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.531

Gnomad SAS AF: 0.334

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.453

Gnomad OTH AF: 0.416

GnomAD4 exome AF: 0.417 AC: 9817 AN: 23550 Hom.: 2200 Cov.: 0 AF XY: 0.413 AC XY: 4445 AN XY: 10762

African (AFR) AF: 0.357 AC: 291 AN: 816

American (AMR) AF: 0.510 AC: 252 AN: 494

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 573 AN: 1484

East Asian (EAS) AF: 0.480 AC: 2397 AN: 4990

South Asian (SAS) AF: 0.321 AC: 61 AN: 190

European-Finnish (FIN) AF: 0.286 AC: 4 AN: 14

Middle Eastern (MID) AF: 0.195 AC: 32 AN: 164

European-Non Finnish (NFE) AF: 0.403 AC: 5419 AN: 13456

Other (OTH) AF: 0.406 AC: 788 AN: 1942

GnomAD4 genome AF: 0.436 AC: 64497 AN: 147986 Hom.: 14326 Cov.: 24 AF XY: 0.437 AC XY: 31382 AN XY: 71852

African (AFR) AF: 0.376 AC: 15081 AN: 40078

American (AMR) AF: 0.519 AC: 7638 AN: 14714

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1396 AN: 3458

East Asian (EAS) AF: 0.531 AC: 2665 AN: 5020

South Asian (SAS) AF: 0.333 AC: 1568 AN: 4708

European-Finnish (FIN) AF: 0.452 AC: 4258 AN: 9418

Middle Eastern (MID) AF: 0.278 AC: 80 AN: 288

European-Non Finnish (NFE) AF: 0.453 AC: 30491 AN: 67364

Other (OTH) AF: 0.414 AC: 842 AN: 2032

Alfa AF: 0.441 Hom.: 2440

Bravo AF: 0.441

Asia WGS AF: 0.410 AC: 1425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.54
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: rs11226; hg19: chr12-1021813;