chr15-40729620-C-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4BP6_ModerateBP7

The NM_002875.5(RAD51):c.760C>A(p.Arg254Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,802 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

RAD51
NM_002875.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.23

Publications

5 publications found

Variant links:

Genes affected

RAD51 (HGNC:9817): (RAD51 recombinase) The protein encoded by this gene is a member of the RAD51 protein family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51, and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with the ssDNA-binding protein RPA and RAD52, and it is thought to play roles in homologous pairing and strand transfer of DNA. This protein is also found to interact with BRCA1 and BRCA2, which may be important for the cellular response to DNA damage. BRCA2 is shown to regulate both the intracellular localization and DNA-binding ability of this protein. Loss of these controls following BRCA2 inactivation may be a key event leading to genomic instability and tumorigenesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2009]

RAD51 Gene-Disease associations (from GenCC):

Fanconi anemia complementation group R
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
mirror movements 2
Inheritance: AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
familial congenital mirror movements
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Fanconi anemia
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
hereditary breast carcinoma
Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

RAD51 links:

Genome browser will be placed here

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=-0.14).

BP6

Variant 15-40729620-C-A is Benign according to our data. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr15-40729620-C-A is described in CliVar as Likely_benign. Clinvar id is 3702368.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=3.23 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51	NM_002875.5 link	c.760C>A	p.Arg254Arg	synonymous_variant	Exon 8 of 10	ENST00000267868.8	NP_002866.2	Q06609-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RAD51	ENST00000267868.8 link	c.760C>A	p.Arg254Arg	synonymous_variant	Exon 8 of 10	1	NM_002875.5	ENSP00000267868.3	Q06609-1
RAD51	ENST00000532743.6 link	c.760C>A	p.Arg254Arg	synonymous_variant	Exon 8 of 10	2		ENSP00000433924.2	Q06609-1
RAD51	ENST00000557850.5 link	c.469C>A	p.Arg157Arg	synonymous_variant	Exon 6 of 8	2		ENSP00000454176.1	Q06609-2

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152114

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000398

AC:

AN:

251486

AF XY:

0.00000736

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:

0.00000879

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1461688

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

727138

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44722

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:

86232

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53418

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5636

European-Non Finnish (NFE)

AF:

0.0000153

AC:

AN:

1111992

Other (OTH)

AF:

0.0000331

AC:

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

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

AF:

0.0000329

AC:

AN:

152114

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74300

show subpopulations

African (AFR)

AF:

0.0000483

AC:

AN:

41426

American (AMR)

AF:

0.00

AC:

AN:

15254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000302

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 06, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.14

CADD

Benign

8.6

(source)

DANN

Benign

0.68

PhyloP100

3.2

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over