rs9901455

chr17-35118530-G-Achr17-35118530-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_002878.4(RAD51D):c.234C>T(p.Ser78=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: 1.68

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]

RAD51L3-RFFL (HGNC:):

ACMG classification

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	UniProt
RAD51D	NM_002878.4	c.234C>T	p.Ser78=	synonymous_variant	3/10	ENST00000345365.11
RAD51L3-RFFL	NR_037714.1	n.232+2761C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD51D	ENST00000345365.11	c.234C>T	p.Ser78=	synonymous_variant	3/10	1	NM_002878.4	P1

Frequencies

GnomAD3 genomes AF: 0.156 AC: 23683 AN: 152030 Hom.: 2577 Cov.: 32

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

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.: 33 AF XY: 0.0901 AC XY: 65551 AN XY: 727166

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.: 32 AF XY: 0.157 AC XY: 11649 AN XY: 74406

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:10

Revision: criteria provided, multiple submitters, no conflicts

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	Invitae	Feb 01, 2024	- -
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. -

Hereditary cancer-predisposing syndrome Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Color Diagnostics, LLC DBA Color Health	Mar 31, 2015	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
Cadd	Benign	12
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

Other links and lift over

dbSNP: rs9901455; hg19: chr17-33445549; COSMIC: COSV99338663; COSMIC: COSV99338663;