Genetic Variant NM_134424.4:c.1037C>T (chr12-914052-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_134424.4(RAD52):c.1037C>T(p.Ser346Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

RAD52
NM_134424.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.103

Publications

37 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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03757271).

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	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD52	NM_134424.4	MANE Select	c.1037C>T	p.Ser346Leu	missense	Exon 11 of 12	NP_602296.2	Q5DR82
RAD52	NM_001297419.1		c.1037C>T	p.Ser346Leu	missense	Exon 11 of 12	NP_001284348.1	Q5DR82
RAD52	NM_001297421.2		c.806C>T	p.Ser269Leu	missense	Exon 9 of 10	NP_001284350.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RAD52	ENST00000358495.8	TSL:1 MANE Select	c.1037C>T	p.Ser346Leu	missense	Exon 11 of 12	ENSP00000351284.3	P43351-1
RAD52	ENST00000430095.6	TSL:1	c.1037C>T	p.Ser346Leu	missense	Exon 11 of 12	ENSP00000387901.2	P43351-1
RAD52	ENST00000461568.5	TSL:1	n.*875C>T		non_coding_transcript_exon	Exon 12 of 12	ENSP00000436008.1	P43351-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000401

AC:

AN:

249554

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727246

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000719

AC:

AN:

1112010

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.053

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.75

CADD

Benign

0.86

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.040

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.38

M_CAP

Benign

0.0022

MetaRNN

Benign

0.038

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.81

PhyloP100

0.10

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.38

REVEL

Benign

0.013

Sift

Benign

0.35

Sift4G

Benign

0.32

Polyphen

0.0

Vest4

0.060

MutPred

0.19

Loss of glycosylation at S346 (P = 0.0196)

MVP

0.26

MPC

0.10

ClinPred

0.032

GERP RS

-2.1

Varity_R

0.028

gMVP

0.057

Mutation Taster

=96/4

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over