chr12-913075-C-T

Variant names:

• chr12-913075-C-T
• rs104895066
• NM_134424.4:c.*316G>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.*316G>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 0.427 in 151,648 control chromosomes in the GnomAD database, including 14,149 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 0.43 (14149 hom., cov: 31)
  • Exomes 𝑓: 0.43 (13034 hom.)
  • Failed GnomAD Quality Control
• Consequence: RAD52 NM_134424.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.819
• Publications: 2 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=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.513 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.*316G>A		3_prime_UTR	Exon 12 of 12	NP_602296.2	Q5DR82
	RAD52	NM_001297419.1		c.*316G>A		3_prime_UTR	Exon 12 of 12	NP_001284348.1	Q5DR82
	RAD52	NM_001297421.2		c.*316G>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.*316G>A		3_prime_UTR	Exon 12 of 12	ENSP00000351284.3	P43351-1
	RAD52	ENST00000430095.6	TSL:1	c.*316G>A		3_prime_UTR	Exon 12 of 12	ENSP00000387901.2	P43351-1
	RAD52	ENST00000904782.1		c.*316G>A		3_prime_UTR	Exon 12 of 12	ENSP00000574841.1

Frequencies

GnomAD3 genomes AF: 0.427 AC: 64708 AN: 151530 Hom.: 14131 Cov.: 31

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.530

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.446

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.452

Gnomad OTH AF: 0.409

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.433 AC: 58524 AN: 135126 Hom.: 13034 Cov.: 0 AF XY: 0.428 AC XY: 28391 AN XY: 66334

African (AFR) AF: 0.346 AC: 1756 AN: 5080

American (AMR) AF: 0.520 AC: 2361 AN: 4544

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 2605 AN: 6390

East Asian (EAS) AF: 0.500 AC: 6675 AN: 13346

South Asian (SAS) AF: 0.287 AC: 1192 AN: 4150

European-Finnish (FIN) AF: 0.421 AC: 1914 AN: 4542

Middle Eastern (MID) AF: 0.264 AC: 204 AN: 774

European-Non Finnish (NFE) AF: 0.435 AC: 37561 AN: 86404

Other (OTH) AF: 0.430 AC: 4256 AN: 9896

GnomAD4 genome AF: 0.427 AC: 64756 AN: 151648 Hom.: 14149 Cov.: 31 AF XY: 0.428 AC XY: 31692 AN XY: 74072

African (AFR) AF: 0.349 AC: 14418 AN: 41352

American (AMR) AF: 0.513 AC: 7809 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3470

East Asian (EAS) AF: 0.530 AC: 2724 AN: 5144

South Asian (SAS) AF: 0.336 AC: 1619 AN: 4816

European-Finnish (FIN) AF: 0.446 AC: 4656 AN: 10450

Middle Eastern (MID) AF: 0.264 AC: 77 AN: 292

European-Non Finnish (NFE) AF: 0.452 AC: 30717 AN: 67888

Other (OTH) AF: 0.407 AC: 855 AN: 2102

Alfa AF: 0.445 Hom.: 1658

Asia WGS AF: 0.409 AC: 1422 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.3
DANN	Benign	0.58
PhyloP100		0.82
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: rs104895066; hg19: chr12-1022241; COSMIC: COSV57273741; COSMIC: COSV57273741;