rs28363302

Variant names:

• chr17-58694224-AC-A
• rs28363302
• NM_058216.3:c.146-705delC

Your query was ambiguous. Multiple possible variants found:

• chr17-58694224-AC-A
• chr17-58694224-AC-ACC

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_058216.3(RAD51C):​c.146-705delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,214 control chromosomes in the GnomAD database, including 2,491 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (2491 hom., cov: 30)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: RAD51C NM_058216.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.129
• Publications: 3 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):

• RAD51C-related cancer predisposition

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• breast-ovarian cancer, familial, susceptibility to, 3

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

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

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.298 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_058216.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	NM_058216.3	MANE Select	c.146-705delC		intron	N/A	NP_478123.1	O43502-1
	RAD51C	NM_002876.4		c.146-705delC		intron	N/A	NP_002867.1	O43502-2
	RAD51C	NR_103872.2		n.188-705delC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD51C	ENST00000337432.9	TSL:1 MANE Select	c.146-705delC		intron	N/A	ENSP00000336701.4	O43502-1
	RAD51C	ENST00000421782.3	TSL:1	c.146-705delC		intron	N/A	ENSP00000391450.2	O43502-2
	RAD51C	ENST00000482007.5	TSL:1	n.146-705delC		intron	N/A	ENSP00000433332.1	Q7KZJ0

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22145 AN: 152040 Hom.: 2484 Cov.: 30

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.0318

Gnomad AMR AF: 0.0785

Gnomad ASJ AF: 0.0856

Gnomad EAS AF: 0.312

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.0951

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0665

Gnomad OTH AF: 0.117

GnomAD4 exome AF: 0.107 AC: 6 AN: 56 Hom.: 0 Cov.: 0 AF XY: 0.0909 AC XY: 2 AN XY: 22

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.167 AC: 1 AN: 6

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.100 AC: 5 AN: 50

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.146 AC: 22179 AN: 152158 Hom.: 2491 Cov.: 30 AF XY: 0.148 AC XY: 11021 AN XY: 74370

African (AFR) AF: 0.289 AC: 11980 AN: 41482

American (AMR) AF: 0.0786 AC: 1200 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0856 AC: 297 AN: 3470

East Asian (EAS) AF: 0.311 AC: 1615 AN: 5192

South Asian (SAS) AF: 0.255 AC: 1229 AN: 4828

European-Finnish (FIN) AF: 0.0951 AC: 1007 AN: 10588

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0665 AC: 4525 AN: 68008

Other (OTH) AF: 0.127 AC: 268 AN: 2108

Alfa AF: 0.110 Hom.: 172

Bravo AF: 0.149

Asia WGS AF: 0.286 AC: 990 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.13
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: rs28363302; hg19: chr17-56771585;