chr12-914296-C-A

Variant names:

• chr12-914296-C-A
• rs104895068
• NM_134424.4:c.967+135G>T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_134424.4(RAD52):​c.967+135G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00521 in 1,370,988 control chromosomes in the GnomAD database, including 21 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.0032 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0055 (20 hom.)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 0.732
• Publications: 1 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BS2: High Homozygotes in GnomAdExome4 at 20 gene

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.967+135G>T		intron	N/A	NP_602296.2	Q5DR82
	RAD52	NM_001297419.1		c.967+135G>T		intron	N/A	NP_001284348.1	Q5DR82
	RAD52	NM_001297421.2		c.736+135G>T		intron	N/A	NP_001284350.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD52	ENST00000358495.8	TSL:1 MANE Select	c.967+135G>T		intron	N/A	ENSP00000351284.3	P43351-1
	RAD52	ENST00000430095.6	TSL:1	c.967+135G>T		intron	N/A	ENSP00000387901.2	P43351-1
	RAD52	ENST00000461568.5	TSL:1	n.*805+135G>T		intron	N/A	ENSP00000436008.1	P43351-3

Frequencies

GnomAD3 genomes AF: 0.00317 AC: 482 AN: 152140 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000990

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00207

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00497

Gnomad OTH AF: 0.00478

GnomAD4 exome AF: 0.00546 AC: 6659 AN: 1218730 Hom.: 20 Cov.: 18 AF XY: 0.00538 AC XY: 3246 AN XY: 603334

African (AFR) AF: 0.000779 AC: 21 AN: 26970

American (AMR) AF: 0.00510 AC: 130 AN: 25468

Ashkenazi Jewish (ASJ) AF: 0.00310 AC: 64 AN: 20644

East Asian (EAS) AF: 0.00 AC: 0 AN: 34976

South Asian (SAS) AF: 0.00185 AC: 123 AN: 66452

European-Finnish (FIN) AF: 0.000556 AC: 20 AN: 35968

Middle Eastern (MID) AF: 0.00463 AC: 24 AN: 5182

European-Non Finnish (NFE) AF: 0.00629 AC: 5985 AN: 951300

Other (OTH) AF: 0.00564 AC: 292 AN: 51770

GnomAD4 genome AF: 0.00317 AC: 482 AN: 152258 Hom.: 1 Cov.: 32 AF XY: 0.00285 AC XY: 212 AN XY: 74444

African (AFR) AF: 0.000987 AC: 41 AN: 41548

American (AMR) AF: 0.00445 AC: 68 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00317 AC: 11 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00207 AC: 10 AN: 4820

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10602

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.00497 AC: 338 AN: 68030

Other (OTH) AF: 0.00473 AC: 10 AN: 2112

Alfa AF: 0.00325 Hom.: 1

Bravo AF: 0.00351

ClinVar

ClinVar submissions

Significance: not provided

Revision: no classification provided

Pathogenic	VUS	Benign	Condition
-	-	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.8
DANN	Benign	0.52
PhyloP100		0.73
Mutation Taster		=100/0	polymorphism

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: rs104895068; hg19: chr12-1023462;