12-917153-T-C

Position:

• chr12-917153-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_134424.4(RAD52):​c.544-333A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.07 in 152,214 control chromosomes in the GnomAD database, including 442 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 0.070 (442 hom., cov: 32)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0836 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD52	NM_134424.4	c.544-333A>G		intron_variant		ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.544-333A>G		intron_variant		1	NM_134424.4	ENSP00000351284	P2

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 10638 AN: 152096 Hom.: 440 Cov.: 32

Gnomad AFR AF: 0.0858

Gnomad AMI AF: 0.132

Gnomad AMR AF: 0.0654

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.000578

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0751

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0809

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0700 AC: 10655 AN: 152214 Hom.: 442 Cov.: 32 AF XY: 0.0692 AC XY: 5152 AN XY: 74422

Gnomad4 AFR AF: 0.0860

Gnomad4 AMR AF: 0.0652

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0110

Gnomad4 FIN AF: 0.0751

Gnomad4 NFE AF: 0.0670

Gnomad4 OTH AF: 0.0806

Alfa AF: 0.0709 Hom.: 43

Bravo AF: 0.0716

Asia WGS AF: 0.0150 AC: 54 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	6.5
DANN	Benign	0.46

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

Publications

LitVar

Other links and lift over

dbSNP: rs11571461; hg19: chr12-1026319;