chr5-69413682-G-T

Variant names:

• chr5-69413682-G-T
• rs299086
• NM_133338.3:c.1752-349G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_133338.3(RAD17):​c.1752-349G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,742 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
• Consequence: RAD17 NM_133338.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.45
• Publications: 4 publications found

Genes affected

RAD17 (HGNC:9807): (RAD17 checkpoint clamp loader component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad17, a cell cycle checkpoint gene required for cell cycle arrest and DNA damage repair in response to DNA damage. This protein shares strong similarity with DNA replication factor C (RFC), and can form a complex with RFCs. This protein binds to chromatin prior to DNA damage and is phosphorylated by the checkpoint kinase ATR following damage. This protein recruits the RAD1-RAD9-HUS1 checkpoint protein complex onto chromatin after DNA damage, which may be required for its phosphorylation. The phosphorylation of this protein is required for the DNA-damage-induced cell cycle G2 arrest, and is thought to be a critical early event during checkpoint signaling in DNA-damaged cells. Multiple alternatively spliced transcript variants of this gene, which encode four distinct protein isoforms, have been reported. Two pseudogenes, located on chromosomes 7 and 13, have been identified. [provided by RefSeq, Jul 2013]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133338.3. 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
	RAD17	NM_133338.3	MANE Select	c.1752-349G>T		intron	N/A	NP_579916.1	O75943-2
	RAD17	NM_133339.2		c.1785-349G>T		intron	N/A	NP_579917.1	O75943-1
	RAD17	NM_001278622.1		c.1752-349G>T		intron	N/A	NP_001265551.1	O75943-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD17	ENST00000354868.10	TSL:1 MANE Select	c.1752-349G>T		intron	N/A	ENSP00000346938.5	O75943-2
	RAD17	ENST00000380774.7	TSL:1	c.1785-349G>T		intron	N/A	ENSP00000370151.3	O75943-1
	RAD17	ENST00000305138.8	TSL:1	c.1752-349G>T		intron	N/A	ENSP00000303134.4	O75943-2

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151742 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151742 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74062

African (AFR) AF: 0.00 AC: 0 AN: 41308

American (AMR) AF: 0.0000656 AC: 1 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5128

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10532

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67928

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.00 Hom.: 1167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.098
DANN	Benign	0.34
PhyloP100		-1.4

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: rs299086; hg19: chr5-68709509;