rs374449943

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 2P and 12B. PM2BP4_StrongBP6_Very_Strong

The NM_002878.4(RAD51D):c.904-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,612,038 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RAD51D
NM_002878.4 intron

Scores

Splicing: ADA: 0.00006361

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 0.0910

Publications

0 publications found

Variant links:

Genes affected

RAD51D (HGNC:9823): (RAD51 paralog D) 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, which are known to be involved in the homologous recombination and repair of DNA. This protein forms a complex with several other members of the RAD51 family, including RAD51L1, RAD51L2, and XRCC2. The protein complex formed with this protein has been shown to catalyze homologous pairing between single- and double-stranded DNA, and is thought to play a role in the early stage of recombinational repair of DNA. Alternative splicing results in multiple transcript variants. Read-through transcription also exists between this gene and the downstream ring finger and FYVE-like domain containing 1 (RFFL) gene. [provided by RefSeq, Jan 2011]

RAD51D Gene-Disease associations (from GenCC):

breast-ovarian cancer, familial, susceptibility to, 4
Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hereditary breast ovarian cancer syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hereditary breast carcinoma
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

RAD51D links:

ENSG00000267618 (HGNC:):

ENSG00000267618 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 17-35101047-A-G is Benign according to our data. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35101047-A-G is described in CliVar as Likely_benign. Clinvar id is 920351.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51D	NM_002878.4 link	c.904-11T>C		intron_variant	Intron 9 of 9	ENST00000345365.11	NP_002869.3	O75771-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51D	ENST00000345365.11 link	c.904-11T>C		intron_variant	Intron 9 of 9	1	NM_002878.4	ENSP00000338790.6		O75771-1
ENSG00000267618	ENST00000593039.5 link	c.426+154T>C		intron_variant	Intron 5 of 6	2		ENSP00000466834.1		K7EN88

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152150

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000795

AC:

AN:

251482

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.000123

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1459770

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726346

show subpopulations

African (AFR)

AF:

0.0000598

AC:

AN:

33418

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26120

East Asian (EAS)

AF:

0.00

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86220

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53416

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110102

Other (OTH)

AF:

0.00

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.0000131

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74450

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41542

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68016

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 4

Benign:2

Jun 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 25, 2025

Myriad Genetics, Inc.

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign. This variant is intronic and is not expected to impact mRNA splicing. -

Hereditary cancer-predisposing syndrome

Benign:1

Jan 04, 2019

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary breast ovarian cancer syndrome

Benign:1

Aug 16, 2023

Department of Pathology and Laboratory Medicine, Sinai Health System

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

-0.83

CADD

Benign

5.4

(source)

DANN

Benign

0.67

PhyloP100

0.091

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000064

dbscSNV1_RF

Benign

0.0080

SpliceAI score (max)

0.13

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