17-35116913-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The ENST00000585343.5(RAD51D):n.*31A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0018 in 1,607,540 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0019 ( 7 hom. )

Consequence

RAD51D
ENST00000585343.5 non_coding_transcript_exon

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: -0.771

Publications

10 publications found

Variant links:

COSMIC-nc: COSV104549250

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007933468).

BP6

Variant 17-35116913-T-C is Benign according to our data. Variant chr17-35116913-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 138879.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00114 (174/152306) while in subpopulation NFE AF = 0.00198 (135/68020). AF 95% confidence interval is 0.00171. There are 0 homozygotes in GnomAd4. There are 78 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 174 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51D	NM_002878.4 link	c.263+1588A>G		intron_variant	Intron 3 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.263+1588A>G		intron_variant	Intron 3 of 9	1	NM_002878.4	ENSP00000338790.6		O75771-1
ENSG00000267618	ENST00000593039.5 link	c.3+4378A>G		intron_variant	Intron 1 of 6	2		ENSP00000466834.1		K7EN88

Frequencies

GnomAD3 genomes

AF:

0.00114

AC:

174

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.000994

AC:

235

AN:

236304

AF XY:

0.000905

show subpopulations

Gnomad AFR exome

AF:

0.000348

Gnomad AMR exome

AF:

0.000362

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000708

Gnomad NFE exome

AF:

0.00187

Gnomad OTH exome

AF:

0.000863

GnomAD4 exome

AF:

0.00186

AC:

2713

AN:

1455234

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

1270

AN XY:

723196

show subpopulations

African (AFR)

AF:

0.000271

AC:

AN:

33268

American (AMR)

AF:

0.000688

AC:

AN:

43592

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25930

East Asian (EAS)

AF:

0.00

AC:

AN:

39460

South Asian (SAS)

AF:

0.0000705

AC:

AN:

85072

European-Finnish (FIN)

AF:

0.000959

AC:

AN:

53170

Middle Eastern (MID)

AF:

0.000174

AC:

AN:

5758

European-Non Finnish (NFE)

AF:

0.00230

AC:

2552

AN:

1108780

Other (OTH)

AF:

0.00106

AC:

AN:

60204

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

140

279

419

558

698

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

196

294

392

490

<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:

0.00114

AC:

174

AN:

152306

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.000457

AC:

AN:

41560

American (AMR)

AF:

0.000588

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.000753

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00198

AC:

135

AN:

68020

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.00178

Hom.:

Bravo

AF:

0.00113

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.000319

AC:

ESP6500EA

AF:

0.00251

AC:

ExAC

AF:

0.00105

AC:

127

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:12

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Breast-ovarian cancer, familial, susceptibility to, 4

Benign:5

Jul 17, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

May 28, 2019

Mendelics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 09, 2016

Counsyl

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com. -

Nov 07, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Dec 14, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hereditary cancer-predisposing syndrome

Benign:3

Aug 26, 2020

Sema4, Sema4

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:curation

- -

Feb 27, 2018

True Health Diagnostics

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jan 20, 2015

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Nov 03, 2021

Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

RAD51D: BP4, BS1 -

not specified

Benign:1

Jan 17, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

RAD51D-related disorder

Benign:1

May 15, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.72

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.0

(source)

DANN

Benign

0.92

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.025

LIST_S2

Benign

0.39

M_CAP

Benign

0.0088

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.96

PhyloP100

-0.77

Sift4G

Benign

0.16

Vest4

0.20

MVP

0.31

MPC

0.21

ClinPred

0.0038

GERP RS

-3.4

gMVP

0.35

Mutation Taster

=92/8

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over