chr17-58692618-C-T

Position:

• chr17-58692618-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_058216.3(RAD51C):​c.-26C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,612,988 control chromosomes in the GnomAD database, including 34,610 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2768 hom., cov: 32)
  • Exomes 𝑓: 0.20 (31842 hom.)
• Consequence: RAD51C NM_058216.3 5_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.24

Genes affected

RAD51C (HGNC:9820): (RAD51 paralog C) This gene is a member of the RAD51 family. RAD51 family members are highly similar to bacterial RecA and Saccharomyces cerevisiae Rad51 and are known to be involved in the homologous recombination and repair of DNA. This protein can interact with other RAD51 paralogs and is reported to be important for Holliday junction resolution. Mutations in this gene are associated with Fanconi anemia-like syndrome. This gene is one of four localized to a region of chromosome 17q23 where amplification occurs frequently in breast tumors. Overexpression of the four genes during amplification has been observed and suggests a possible role in tumor progression. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BP6: Variant 17-58692618-C-T is Benign according to our data. Variant chr17-58692618-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 324173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-58692618-C-T is described in Lovd as [Likely_benign]. Variant chr17-58692618-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51C	NM_058216.3	c.-26C>T		5_prime_UTR_variant	1/9	ENST00000337432.9	NP_478123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9	c.-26C>T		5_prime_UTR_variant	1/9	1	NM_058216.3	ENSP00000336701	P2

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28080 AN: 152098 Hom.: 2765 Cov.: 32

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.323

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.264

Gnomad MID AF: 0.0828

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.169

GnomAD3 exomes AF: 0.180 AC: 44995 AN: 250272 Hom.: 4419 AF XY: 0.179 AC XY: 24213 AN XY: 135486

Gnomad AFR exome AF: 0.138

Gnomad AMR exome AF: 0.133

Gnomad ASJ exome AF: 0.0905

Gnomad EAS exome AF: 0.170

Gnomad SAS exome AF: 0.138

Gnomad FIN exome AF: 0.263

Gnomad NFE exome AF: 0.206

Gnomad OTH exome AF: 0.157

GnomAD4 exome AF: 0.204 AC: 298243 AN: 1460772 Hom.: 31842 Cov.: 33 AF XY: 0.202 AC XY: 146701 AN XY: 726612

Gnomad4 AFR exome AF: 0.132

Gnomad4 AMR exome AF: 0.138

Gnomad4 ASJ exome AF: 0.0890

Gnomad4 EAS exome AF: 0.208

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.261

Gnomad4 NFE exome AF: 0.216

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.185 AC: 28097 AN: 152216 Hom.: 2768 Cov.: 32 AF XY: 0.187 AC XY: 13935 AN XY: 74418

Gnomad4 AFR AF: 0.137

Gnomad4 AMR AF: 0.176

Gnomad4 ASJ AF: 0.0824

Gnomad4 EAS AF: 0.177

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.264

Gnomad4 NFE AF: 0.212

Gnomad4 OTH AF: 0.167

Alfa AF: 0.188 Hom.: 747

Bravo AF: 0.170

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics Laboratory, Department of Pathology, Netherlands Cancer Institute	-	- -
Likely benign, no assertion criteria provided	curation	Leiden Open Variation Database	Nov 02, 2014	Curator: Arleen D. Auerbach. Submitter to LOVD: Christine Rappaport. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

not provided Benign:2

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

Fanconi anemia Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

RAD51C-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 09, 2022

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

Breast and Ovarian Cancer Susceptibility Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	0.74
DANN	Benign	0.88

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: rs12946397; hg19: chr17-56769979; COSMIC: COSV53625930; COSMIC: COSV53625930;