rs2921787

Variant names:

• chr8-116857259-C-T
• rs2921787
• NM_006265.3:c.688+8G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-116857259-C-T
• chr8-116857259-C-A
• chr8-116857259-C-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.688+8G>A variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0426 in 1,596,092 control chromosomes in the GnomAD database, including 4,958 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (2052 hom., cov: 33)
  • Exomes 𝑓: 0.035 (2906 hom.)
• Consequence: RAD21 NM_006265.3 splice_region, intron
• Scores: Splicing: ADA: 0.00003647
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.0230
• Publications: 11 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]

RAD21 Gene-Disease associations (from GenCC):

• Cornelia de Lange syndrome

  Inheritance: AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Cornelia de Lange syndrome 4

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• Mungan syndrome

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 8-116857259-C-T is Benign according to our data. Variant chr8-116857259-C-T is described in ClinVar as Benign. ClinVar VariationId is 159808.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.297 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.688+8G>A		splice_region 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.688+8G>A		splice_region intron	N/A	ENSP00000297338.2	O60216
	RAD21	ENST00000517749.2	TSL:1	c.688+8G>A		splice_region intron	N/A	ENSP00000430273.2	O60216
	RAD21	ENST00000517485.6	TSL:3	c.688+8G>A		splice_region intron	N/A	ENSP00000427923.2	O60216

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16796 AN: 152014 Hom.: 2044 Cov.: 33

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.0764

Gnomad ASJ AF: 0.0612

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0114

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0230

Gnomad OTH AF: 0.0956

GnomAD2 exomes AF: 0.0632 AC: 15747 AN: 249250 AF XY: 0.0555

Gnomad AFR exome AF: 0.301

Gnomad AMR exome AF: 0.0864

Gnomad ASJ exome AF: 0.0632

Gnomad EAS exome AF: 0.147

Gnomad FIN exome AF: 0.0153

Gnomad NFE exome AF: 0.0247

Gnomad OTH exome AF: 0.0493

GnomAD4 exome AF: 0.0354 AC: 51096 AN: 1443960 Hom.: 2906 Cov.: 29 AF XY: 0.0346 AC XY: 24896 AN XY: 718980

African (AFR) AF: 0.303 AC: 9932 AN: 32814

American (AMR) AF: 0.0849 AC: 3773 AN: 44444

Ashkenazi Jewish (ASJ) AF: 0.0597 AC: 1551 AN: 25960

East Asian (EAS) AF: 0.164 AC: 6459 AN: 39442

South Asian (SAS) AF: 0.0384 AC: 3293 AN: 85688

European-Finnish (FIN) AF: 0.0156 AC: 827 AN: 52916

Middle Eastern (MID) AF: 0.0875 AC: 359 AN: 4102

European-Non Finnish (NFE) AF: 0.0195 AC: 21442 AN: 1098994

Other (OTH) AF: 0.0581 AC: 3460 AN: 59600

GnomAD4 genome AF: 0.111 AC: 16835 AN: 152132 Hom.: 2052 Cov.: 33 AF XY: 0.108 AC XY: 8042 AN XY: 74376

African (AFR) AF: 0.301 AC: 12478 AN: 41458

American (AMR) AF: 0.0763 AC: 1165 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0612 AC: 212 AN: 3464

East Asian (EAS) AF: 0.154 AC: 799 AN: 5174

South Asian (SAS) AF: 0.0420 AC: 203 AN: 4828

European-Finnish (FIN) AF: 0.0114 AC: 121 AN: 10608

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1563 AN: 68004

Other (OTH) AF: 0.0970 AC: 205 AN: 2114

Alfa AF: 0.0491 Hom.: 1129

Bravo AF: 0.124

Asia WGS AF: 0.115 AC: 398 AN: 3478

EpiCase AF: 0.0268

EpiControl AF: 0.0301

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Cornelia de Lange syndrome 4 (2)
-	-	1	Mungan syndrome (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.44
PhyloP100		0.023
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000036
dbscSNV1_RF	Benign	0.0
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2921787;

hg19: chr8-117869498;

COSMIC: COSV52056585;

COSMIC: COSV52056585;