rs9901455

Positions:

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_002878.4(RAD51D):c.234C>T(p.Ser78Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0971 in 1,613,868 control chromosomes in the GnomAD database, including 10,503 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2581 hom., cov: 32)

Exomes 𝑓: 0.091 ( 7922 hom. )

Consequence

RAD51D
NM_002878.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: 1.68

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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BP6

Variant 17-35118530-G-A is Benign according to our data. Variant chr17-35118530-G-A is described in ClinVar as [Benign]. Clinvar id is 183785.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-35118530-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.67 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.295 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.234C>T	p.Ser78Ser	synonymous_variant	3/10	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.234C>T	p.Ser78Ser	synonymous_variant	3/10	1	NM_002878.4	ENSP00000338790.6		O75771-1
ENSG00000267618	ENST00000593039.5 linkuse as main transcript	c.3+2761C>T		intron_variant		2		ENSP00000466834.1		K7EN88

Frequencies

GnomAD3 genomes

AF:

0.156

AC:

23683

AN:

152030

Hom.:

2577

Cov.:

show subpopulations

Gnomad AFR

AF:

0.300

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.126

Gnomad ASJ

AF:

0.159

Gnomad EAS

AF:

0.227

Gnomad SAS

AF:

0.0864

Gnomad FIN

AF:

0.119

Gnomad MID

AF:

0.130

Gnomad NFE

AF:

0.0827

Gnomad OTH

AF:

0.137

GnomAD3 exomes

AF:

0.116

AC:

29273

AN:

251448

Hom.:

2249

AF XY:

0.111

AC XY:

15077

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.306

Gnomad AMR exome

AF:

0.104

Gnomad ASJ exome

AF:

0.140

Gnomad EAS exome

AF:

0.230

Gnomad SAS exome

AF:

0.0860

Gnomad FIN exome

AF:

0.112

Gnomad NFE exome

AF:

0.0821

Gnomad OTH exome

AF:

0.111

GnomAD4 exome

AF:

0.0910

AC:

133000

AN:

1461720

Hom.:

7922

Cov.:

AF XY:

0.0901

AC XY:

65551

AN XY:

727166

show subpopulations

Gnomad4 AFR exome

AF:

0.304

Gnomad4 AMR exome

AF:

0.107

Gnomad4 ASJ exome

AF:

0.142

Gnomad4 EAS exome

AF:

0.261

Gnomad4 SAS exome

AF:

0.0866

Gnomad4 FIN exome

AF:

0.109

Gnomad4 NFE exome

AF:

0.0752

Gnomad4 OTH exome

AF:

0.104

GnomAD4 genome

AF:

0.156

AC:

23705

AN:

152148

Hom.:

2581

Cov.:

AF XY:

0.157

AC XY:

11649

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.300

Gnomad4 AMR

AF:

0.125

Gnomad4 ASJ

AF:

0.159

Gnomad4 EAS

AF:

0.227

Gnomad4 SAS

AF:

0.0860

Gnomad4 FIN

AF:

0.119

Gnomad4 NFE

AF:

0.0827

Gnomad4 OTH

AF:

0.141

Alfa

AF:

0.112

Hom.:

714

Bravo

AF:

0.162

Asia WGS

AF:

0.147

AC:

513

AN:

3478

EpiCase

AF:

0.0837

EpiControl

AF:

0.0830

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Sep 11, 2015	- -
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+	-	- -

Breast-ovarian cancer, familial, susceptibility to, 4

Benign:3

Benign, criteria provided, single submitter	clinical testing	Counsyl	Jun 28, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Myriad Genetics, Inc.	Apr 06, 2023	This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 01, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -

Hereditary cancer-predisposing syndrome

Benign:2

Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 31, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Ambry Genetics	Oct 25, 2014	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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Benign

0.84

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