rs2289938

Variant names:

• chr8-116849277-T-C
• rs2289938
• NM_006265.3:c.1621-248A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 7 publications found

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]

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]

LOC112268030 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006265.3. 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
	RAD21	NM_006265.3	MANE Select	c.1621-248A>G		intron	N/A	NP_006256.1	O60216

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RAD21	ENST00000297338.7	TSL:1 MANE Select	c.1621-248A>G		intron	N/A	ENSP00000297338.2	O60216
	RAD21	ENST00000517749.2	TSL:1	c.1621-248A>G		intron	N/A	ENSP00000430273.2	O60216
	UTP23	ENST00000517820.1	TSL:3	c.*260T>C		3_prime_UTR	Exon 2 of 2	ENSP00000427767.1	G3XAM4

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

African (AFR) AF: 0.0317 AC: 225 AN: 7094

American (AMR) AF: 0.242 AC: 1822 AN: 7518

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 2043 AN: 9196

East Asian (EAS) AF: 0.160 AC: 3471 AN: 21680

South Asian (SAS) AF: 0.235 AC: 1547 AN: 6592

European-Finnish (FIN) AF: 0.173 AC: 3332 AN: 19234

Middle Eastern (MID) AF: 0.190 AC: 247 AN: 1300

European-Non Finnish (NFE) AF: 0.172 AC: 27171 AN: 158200

Other (OTH) AF: 0.164 AC: 2663 AN: 16286

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

African (AFR) AF: 0.0312 AC: 1293 AN: 41478

American (AMR) AF: 0.211 AC: 3221 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.224 AC: 778 AN: 3472

East Asian (EAS) AF: 0.176 AC: 905 AN: 5152

South Asian (SAS) AF: 0.198 AC: 952 AN: 4808

European-Finnish (FIN) AF: 0.170 AC: 1798 AN: 10584

Middle Eastern (MID) AF: 0.184 AC: 54 AN: 294

European-Non Finnish (NFE) AF: 0.166 AC: 11249 AN: 67920

Other (OTH) AF: 0.136 AC: 286 AN: 2106

Alfa AF: 0.167 Hom.: 1123

Bravo AF: 0.133

Asia WGS AF: 0.179 AC: 623 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.76
DANN	Benign	0.42
PhyloP100		-0.80
Mutation Taster		=298/2	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: rs2289938; hg19: chr8-117861516;