17-58694224-AC-A

Position:

• chr17-58694224-AC-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_058216.3(RAD51C):​c.146-705del 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

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 -8 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RAD51C	NM_058216.3	c.146-705del		intron_variant		ENST00000337432.9	NP_478123.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RAD51C	ENST00000337432.9	c.146-705del		intron_variant		1	NM_058216.3	ENSP00000336701	P2

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

Gnomad4 AMR exome AF: 0.167

Gnomad4 NFE exome AF: 0.100

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

Gnomad4 AFR AF: 0.289

Gnomad4 AMR AF: 0.0786

Gnomad4 ASJ AF: 0.0856

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.255

Gnomad4 FIN AF: 0.0951

Gnomad4 NFE AF: 0.0665

Gnomad4 OTH AF: 0.127

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 v4.3

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: rs28363302; hg19: chr17-56771585;