Genetic Variant NM_134424.4:c.*395G>A (chr12-912996-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_134424.4(RAD52):c.*395G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00611 in 225,378 control chromosomes in the GnomAD database, including 2 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 0.0064 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0056 ( 1 hom. )

Consequence

RAD52
NM_134424.4 3_prime_UTR

Scores

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: -0.307

Publications

2 publications found

Variant links:

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]

RAD52 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD52	NM_134424.4	MANE Select	c.*395G>A	3_prime_UTR	Exon 12 of 12	NP_602296.2	Q5DR82
RAD52	NM_001297419.1		c.*395G>A	3_prime_UTR	Exon 12 of 12	NP_001284348.1	Q5DR82
RAD52	NM_001297421.2		c.*395G>A	3_prime_UTR	Exon 10 of 10	NP_001284350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RAD52	ENST00000358495.8	TSL:1 MANE Select	c.*395G>A	3_prime_UTR	Exon 12 of 12	ENSP00000351284.3	P43351-1
RAD52	ENST00000430095.6	TSL:1	c.*395G>A	3_prime_UTR	Exon 12 of 12	ENSP00000387901.2	P43351-1
RAD52	ENST00000904782.1		c.*395G>A	3_prime_UTR	Exon 12 of 12	ENSP00000574841.1

Frequencies

GnomAD3 genomes

AF:

0.00636

AC:

962

AN:

151262

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00163

Gnomad AMI

AF:

0.0329

Gnomad AMR

AF:

0.00146

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00852

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0111

Gnomad OTH

AF:

0.00193

GnomAD4 exome

AF:

0.00562

AC:

416

AN:

74000

Hom.:

Cov.:

AF XY:

0.00544

AC XY:

189

AN XY:

34744

show subpopulations

African (AFR)

AF:

0.00178

AC:

AN:

3366

American (AMR)

AF:

0.000884

AC:

AN:

2262

Ashkenazi Jewish (ASJ)

AF:

0.000225

AC:

AN:

4446

East Asian (EAS)

AF:

0.00

AC:

AN:

9760

South Asian (SAS)

AF:

0.00

AC:

AN:

816

European-Finnish (FIN)

AF:

0.0128

AC:

AN:

468

Middle Eastern (MID)

AF:

0.00

AC:

AN:

454

European-Non Finnish (NFE)

AF:

0.00816

AC:

379

AN:

46444

Other (OTH)

AF:

0.00368

AC:

AN:

5984

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

108

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00635

AC:

962

AN:

151378

Hom.:

Cov.:

AF XY:

0.00556

AC XY:

411

AN XY:

73910

show subpopulations

African (AFR)

AF:

0.00162

AC:

AN:

41304

American (AMR)

AF:

0.00146

AC:

AN:

15120

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4782

European-Finnish (FIN)

AF:

0.00852

AC:

AN:

10448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0111

AC:

750

AN:

67806

Other (OTH)

AF:

0.00191

AC:

AN:

2096

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

143

191

239

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00815

Hom.:

Bravo

AF:

0.00544

ClinVar

ClinVar submissions

Significance:not provided

Revision:no classification provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.46

PhyloP100

-0.31

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over