rs2289938

Positions:

• chr8-116849277-T-C

Variant summary

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

The NM_006265.3(RAD21):​c.1621-248A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 399,088 control chromosomes in the GnomAD database, including 5,642 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1758 hom., cov: 32)
  • Exomes 𝑓: 0.17 (3884 hom.)
• Consequence: RAD21 NM_006265.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.802

Genes affected

RAD21 (HGNC:9811): (RAD21 cohesin complex component) The protein encoded by this gene is highly similar to the gene product of Schizosaccharomyces pombe rad21, a gene involved in the repair of DNA double-strand breaks, as well as in chromatid cohesion during mitosis. This protein is a nuclear phospho-protein, which becomes hyperphosphorylated in cell cycle M phase. The highly regulated association of this protein with mitotic chromatin specifically at the centromere region suggests its role in sister chromatid cohesion in mitotic cells. [provided by RefSeq, Jul 2008]

LOC112268030 (HGNC:):

UTP23 (HGNC:28224): (UTP23 small subunit processome component) Enables mRNA 3'-UTR binding activity and mRNA 5'-UTR binding activity. Predicted to be involved in rRNA processing. Predicted to act upstream of or within endonucleolytic cleavage in 5'-ETS of tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA). Predicted to be part of small-subunit processome. Predicted to be active in nucleolus. Implicated in colorectal adenocarcinoma. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-116849277-T-C is Benign according to our data. Variant chr8-116849277-T-C is described in ClinVar as [Benign]. Clinvar id is 669106.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.205 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RAD21	NM_006265.3	c.1621-248A>G		intron_variant		ENST00000297338.7
LOC112268030	XR_002956724.2	n.1150T>C		non_coding_transcript_exon_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RAD21	ENST00000297338.7	c.1621-248A>G		intron_variant		1	NM_006265.3	P1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20609 AN: 151870 Hom.: 1755 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.211

Gnomad ASJ AF: 0.224

Gnomad EAS AF: 0.175

Gnomad SAS AF: 0.199

Gnomad FIN AF: 0.170

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.134

GnomAD4 exome AF: 0.172 AC: 42521 AN: 247100 Hom.: 3884 Cov.: 0 AF XY: 0.174 AC XY: 22024 AN XY: 126584

Gnomad4 AFR exome AF: 0.0317

Gnomad4 AMR exome AF: 0.242

Gnomad4 ASJ exome AF: 0.222

Gnomad4 EAS exome AF: 0.160

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.173

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.164

GnomAD4 genome AF: 0.136 AC: 20622 AN: 151988 Hom.: 1758 Cov.: 32 AF XY: 0.139 AC XY: 10303 AN XY: 74288

Gnomad4 AFR AF: 0.0312

Gnomad4 AMR AF: 0.211

Gnomad4 ASJ AF: 0.224

Gnomad4 EAS AF: 0.176

Gnomad4 SAS AF: 0.198

Gnomad4 FIN AF: 0.170

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.136

Alfa AF: 0.168 Hom.: 1005

Bravo AF: 0.133

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.42

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: rs2289938; hg19: chr8-117861516;