12-916689-AG-GA

Variant names:

• chr12-916689-AG-GA
• NM_134424.4:c.674_675delCTinsTC
• RAD52 p.Pro225Leu

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_134424.4(RAD52):​c.674_675delCTinsTC​(p.Pro225Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RAD52 NM_134424.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

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.674_675delCTinsTC	p.Pro225Leu	missense	N/A	NP_602296.2	Q5DR82
	RAD52	NM_001297419.1		c.674_675delCTinsTC	p.Pro225Leu	missense	N/A	NP_001284348.1	Q5DR82
	RAD52	NM_001297421.2		c.443_444delCTinsTC	p.Pro148Leu	missense	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.674_675delCTinsTC	p.Pro225Leu	missense	N/A	ENSP00000351284.3	P43351-1
	RAD52	ENST00000430095.6	TSL:1	c.674_675delCTinsTC	p.Pro225Leu	missense	N/A	ENSP00000387901.2	P43351-1
	RAD52	ENST00000461568.5	TSL:1	n.*460_*461delCTinsTC		non_coding_transcript_exon	Exon 9 of 12	ENSP00000436008.1	P43351-3

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-1025855;