chr12-955272-T-C

Variant names:

• chr12-955272-T-C
• rs10849605
• ENST00000430095.6:c.-18-22196A>G

Variant summary

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

The ENST00000430095.6(RAD52):​c.-18-22196A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.488 in 151,956 control chromosomes in the GnomAD database, including 18,233 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 0.49 (18233 hom., cov: 31)
• Consequence: RAD52 ENST00000430095.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00900
• Publications: 28 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]

ENSG00000299067 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.522 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD52	NM_001297419.1	c.-18-22196A>G		intron_variant	Intron 1 of 11		NP_001284348.1
RAD52	XM_005253720.6	c.-18-22196A>G		intron_variant	Intron 2 of 12		XP_005253777.1
RAD52	XM_017019769.2	c.-18-22196A>G		intron_variant	Intron 2 of 12		XP_016875258.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD52	ENST00000430095.6	c.-18-22196A>G		intron_variant	Intron 1 of 11	1		ENSP00000387901.2
ENSG00000299067	ENST00000760288.1	n.90-2619T>C		intron_variant	Intron 1 of 2
ENSG00000299067	ENST00000760289.1	n.134-2619T>C		intron_variant	Intron 1 of 2

Frequencies

GnomAD3 genomes AF: 0.488 AC: 74059 AN: 151840 Hom.: 18228 Cov.: 31

Gnomad AFR AF: 0.455

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.428

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.439

Gnomad NFE AF: 0.527

Gnomad OTH AF: 0.479

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

GnomAD4 genome AF: 0.488 AC: 74097 AN: 151956 Hom.: 18233 Cov.: 31 AF XY: 0.485 AC XY: 36000 AN XY: 74268

African (AFR) AF: 0.454 AC: 18825 AN: 41440

American (AMR) AF: 0.509 AC: 7757 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.428 AC: 1485 AN: 3470

East Asian (EAS) AF: 0.341 AC: 1766 AN: 5176

South Asian (SAS) AF: 0.474 AC: 2286 AN: 4818

European-Finnish (FIN) AF: 0.444 AC: 4681 AN: 10554

Middle Eastern (MID) AF: 0.442 AC: 129 AN: 292

European-Non Finnish (NFE) AF: 0.527 AC: 35787 AN: 67944

Other (OTH) AF: 0.480 AC: 1011 AN: 2106

Alfa AF: 0.508 Hom.: 42860

Bravo AF: 0.489

Asia WGS AF: 0.414 AC: 1441 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.45
DANN	Benign	0.72
PhyloP100		-0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10849605; hg19: chr12-1064438;