chr12-922288-G-A

Variant names:

• chr12-922288-G-A
• rs7962050
• NM_134424.4:c.543+3162C>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.543+3162C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.579 in 151,032 control chromosomes in the GnomAD database, including 25,964 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 0.58 (25964 hom., cov: 28)
• Consequence: RAD52 NM_134424.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.918
• Publications: 9 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_134424.4	c.543+3162C>T		intron_variant	Intron 7 of 11	ENST00000358495.8	NP_602296.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000358495.8	c.543+3162C>T		intron_variant	Intron 7 of 11	1	NM_134424.4	ENSP00000351284.3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 87359 AN: 150926 Hom.: 25945 Cov.: 28

Gnomad AFR AF: 0.459

Gnomad AMI AF: 0.734

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.711

Gnomad SAS AF: 0.516

Gnomad FIN AF: 0.720

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.608

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.579 AC: 87416 AN: 151032 Hom.: 25964 Cov.: 28 AF XY: 0.584 AC XY: 43066 AN XY: 73714

African (AFR) AF: 0.459 AC: 18851 AN: 41082

American (AMR) AF: 0.650 AC: 9864 AN: 15174

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1971 AN: 3462

East Asian (EAS) AF: 0.711 AC: 3657 AN: 5140

South Asian (SAS) AF: 0.516 AC: 2470 AN: 4784

European-Finnish (FIN) AF: 0.720 AC: 7366 AN: 10228

Middle Eastern (MID) AF: 0.503 AC: 147 AN: 292

European-Non Finnish (NFE) AF: 0.608 AC: 41249 AN: 67866

Other (OTH) AF: 0.561 AC: 1176 AN: 2098

Alfa AF: 0.594 Hom.: 33746

Bravo AF: 0.572

Asia WGS AF: 0.574 AC: 1998 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.83
DANN	Benign	0.56
PhyloP100		-0.92
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: rs7962050; hg19: chr12-1031454;