chr17-58725332-G-C

Variant names:

• chr17-58725332-G-C
• rs10515159
• NM_058216.3:c.965+1232G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_058216.3(RAD51C):​c.965+1232G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.185 in 152,000 control chromosomes in the GnomAD database, including 2,788 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.19 (2788 hom., cov: 31)
• Consequence: RAD51C NM_058216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.57
• Publications: 12 publications found

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]

RAD51C Gene-Disease associations (from GenCC):

• breast-ovarian cancer, familial, susceptibility to, 3

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Genomics England PanelApp, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Fanconi anemia complementation group O

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• hereditary breast ovarian cancer syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary breast carcinoma

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

LOC105371843 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD51C	NM_058216.3	c.965+1232G>C		intron_variant	Intron 7 of 8	ENST00000337432.9	NP_478123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9	c.965+1232G>C		intron_variant	Intron 7 of 8	1	NM_058216.3	ENSP00000336701.4

Frequencies

GnomAD3 genomes AF: 0.185 AC: 28148 AN: 151882 Hom.: 2785 Cov.: 31

Gnomad AFR AF: 0.137

Gnomad AMI AF: 0.319

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.0824

Gnomad EAS AF: 0.176

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.213

Gnomad OTH AF: 0.169

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.185 AC: 28165 AN: 152000 Hom.: 2788 Cov.: 31 AF XY: 0.188 AC XY: 13972 AN XY: 74288

African (AFR) AF: 0.137 AC: 5676 AN: 41464

American (AMR) AF: 0.176 AC: 2694 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0824 AC: 286 AN: 3472

East Asian (EAS) AF: 0.177 AC: 913 AN: 5158

South Asian (SAS) AF: 0.139 AC: 672 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2804 AN: 10510

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.213 AC: 14452 AN: 67988

Other (OTH) AF: 0.167 AC: 352 AN: 2114

Alfa AF: 0.200 Hom.: 389

Bravo AF: 0.170

Asia WGS AF: 0.164 AC: 570 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	14
DANN	Benign	0.53
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10515159; hg19: chr17-56802693;