chr8-116852713-T-TAAA

Variant names:

• chr8-116852713-T-TAAA
• rs369816312
• NM_006265.3:c.1162-8_1162-6dupTTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006265.3(RAD21):​c.1162-8_1162-6dupTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000652 in 1,043,296 control chromosomes in the GnomAD database, with no homozygous occurrence. There is a variant allele frequency bias in the population database for this variant (GnomAdExome4), which may indicate mosaicism or somatic mutations in the reference population data. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.000065 (0 hom.)
• Consequence: RAD21 NM_006265.3 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 3 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: Orphanet, ClinGen
• Cornelia de Lange syndrome 4

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

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RAD21	NM_006265.3	c.1162-8_1162-6dupTTT		splice_region_variant, intron_variant	Intron 9 of 13	ENST00000297338.7	NP_006256.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RAD21	ENST00000297338.7	c.1162-8_1162-6dupTTT		splice_region_variant, intron_variant	Intron 9 of 13	1	NM_006265.3	ENSP00000297338.2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.0000574 AC: 5 AN: 87152 AF XY: 0.0000413

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000180

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000676

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000652 AC: 68 AN: 1043296 Hom.: 0 Cov.: 2 AF XY: 0.0000624 AC XY: 32 AN XY: 513034

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000448 AC: 1 AN: 22318

American (AMR) AF: 0.00 AC: 0 AN: 19128

Ashkenazi Jewish (ASJ) AF: 0.000119 AC: 2 AN: 16868

East Asian (EAS) AF: 0.00 AC: 0 AN: 27482

South Asian (SAS) AF: 0.000229 AC: 10 AN: 43698

European-Finnish (FIN) AF: 0.000136 AC: 5 AN: 36768

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3932

European-Non Finnish (NFE) AF: 0.0000578 AC: 48 AN: 830556

Other (OTH) AF: 0.0000470 AC: 2 AN: 42546

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.19

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs369816312; hg19: chr8-117864952;