chr17-35106468-C-T

Position:

chr17-35106468-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002878.4(RAD51D):c.494G>A(p.Arg165Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 1,611,192 control chromosomes in the GnomAD database, including 17,336 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.12 ( 1455 hom., cov: 32)

Exomes 𝑓: 0.14 ( 15881 hom. )

Consequence

RAD51D
NM_002878.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:12

Conservation

PhyloP100: 1.18

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 links:

ENSG00000267618 (HGNC:):

ENSG00000267618 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022848845).

BP6

Variant 17-35106468-C-T is Benign according to our data. Variant chr17-35106468-C-T is described in ClinVar as [Benign]. Clinvar id is 142159.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35106468-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.211 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51D	NM_002878.4 linkuse as main transcript	c.494G>A	p.Arg165Gln	missense_variant	6/10	ENST00000345365.11	NP_002869.3	O75771-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51D	ENST00000345365.11 linkuse as main transcript	c.494G>A	p.Arg165Gln	missense_variant	6/10	1	NM_002878.4	ENSP00000338790.6		O75771-1
ENSG00000267618	ENST00000593039.5 linkuse as main transcript	c.17G>A	p.Arg6Gln	missense_variant	2/7	2		ENSP00000466834.1		K7EN88

Frequencies

GnomAD3 genomes

AF:

0.121

AC:

18421

AN:

152092

Hom.:

1452

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0335

Gnomad AMI

AF:

0.110

Gnomad AMR

AF:

0.217

Gnomad ASJ

AF:

0.205

Gnomad EAS

AF:

0.0458

Gnomad SAS

AF:

0.144

Gnomad FIN

AF:

0.178

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.144

Gnomad OTH

AF:

0.118

GnomAD3 exomes

AF:

0.156

AC:

38415

AN:

247030

Hom.:

3695

AF XY:

0.154

AC XY:

20565

AN XY:

133538

show subpopulations

Gnomad AFR exome

AF:

0.0296

Gnomad AMR exome

AF:

0.295

Gnomad ASJ exome

AF:

0.190

Gnomad EAS exome

AF:

0.0455

Gnomad SAS exome

AF:

0.163

Gnomad FIN exome

AF:

0.169

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.141

AC:

205147

AN:

1458982

Hom.:

15881

Cov.:

AF XY:

0.141

AC XY:

102408

AN XY:

725640

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.285

Gnomad4 ASJ exome

AF:

0.194

Gnomad4 EAS exome

AF:

0.0429

Gnomad4 SAS exome

AF:

0.163

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.138

Gnomad4 OTH exome

AF:

0.135

GnomAD4 genome

AF:

0.121

AC:

18427

AN:

152210

Hom.:

1455

Cov.:

AF XY:

0.125

AC XY:

9284

AN XY:

74424

show subpopulations

Gnomad4 AFR

AF:

0.0335

Gnomad4 AMR

AF:

0.217

Gnomad4 ASJ

AF:

0.205

Gnomad4 EAS

AF:

0.0459

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.178

Gnomad4 NFE

AF:

0.144

Gnomad4 OTH

AF:

0.117

Alfa

AF:

0.138

Hom.:

4163

Bravo

AF:

0.120

TwinsUK

AF:

0.143

AC:

531

ALSPAC

AF:

0.131

AC:

504

ESP6500AA

AF:

0.0368

AC:

162

ESP6500EA

AF:

0.143

AC:

1227

ExAC

AF:

0.148

AC:

17916

Asia WGS

AF:

0.0980

AC:

343

AN:

3478

ClinVar

Significance: 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

Benign, criteria provided, single submitter	clinical testing	Counsyl	Jun 18, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Institute of Human Genetics, University of Leipzig Medical Center	Jan 01, 2019	- -
Benign, criteria provided, single submitter	clinical testing	Myriad Genetics, Inc.	May 10, 2023	This variant is considered benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 28202063) -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Jan 18, 2019	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Nov 05, 2014	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.65

BayesDel_noAF

Benign

-0.56

CADD

Benign

DANN

Benign

0.91

DEOGEN2

Benign

0.074

.;.;T;T;.;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.039

LIST_S2

Benign

0.65

T;T;.;T;T;T;T;T

MetaRNN

Benign

0.0023

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

.;.;N;N;.;.;.;.

PROVEAN

Benign

1.6

.;.;N;D;.;.;.;.

REVEL

Benign

0.13

Sift

Benign

1.0

.;.;T;D;.;.;.;.

Sift4G

Benign

1.0

T;T;T;T;T;T;T;.

Polyphen

0.0, 0.0080

.;.;B;B;B;.;.;.

Vest4

0.080

MPC

0.41

ClinPred

0.0074

GERP RS

0.25

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.029

gMVP

0.051

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over