10-100189834-CTTTTTTTTTT-CTTTTTTTTTTTTTTTTTTTT

Variant names:

• chr10-100189834-C-CTTTTTTTTTT
• rs34571703
• NM_001278.5:c.2209-217_2209-208dupAAAAAAAAAA

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001278.5(CHUK):​c.2209-217_2209-208dupAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000216 in 139,132 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000022 (0 hom., cov: 30)
• Consequence: CHUK NM_001278.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.274
• Publications: 0 publications found

Genes affected

CHUK (HGNC:1974): (component of inhibitor of nuclear factor kappa B kinase complex) This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008]

CHUK Gene-Disease associations (from GenCC):

• cocoon syndrome

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics
• Bartsocas-Papas syndrome 2

  Inheritance: AR Classification: MODERATE Submitted by: ClinGen, Ambry Genetics

ENSG00000236308 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001278.5. 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
	CHUK	NM_001278.5	MANE Select	c.2209-217_2209-208dupAAAAAAAAAA		intron	N/A	NP_001269.3
	CHUK	NM_001441062.1		c.2209-336_2209-327dupAAAAAAAAAA		intron	N/A	NP_001427991.1
	CHUK	NM_001441063.1		c.2208+1025_2208+1034dupAAAAAAAAAA		intron	N/A	NP_001427992.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHUK	ENST00000370397.8	TSL:1 MANE Select	c.2209-208_2209-207insAAAAAAAAAA		intron	N/A	ENSP00000359424.6	O15111
	CHUK	ENST00000590930.5	TSL:1	n.3585-208_3585-207insAAAAAAAAAA		intron	N/A
	CHUK	ENST00000896937.1		c.2203-208_2203-207insAAAAAAAAAA		intron	N/A	ENSP00000566996.1

Frequencies

GnomAD3 genomes AF: 0.0000216 AC: 3 AN: 139118 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000469

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000216 AC: 3 AN: 139132 Hom.: 0 Cov.: 30 AF XY: 0.0000149 AC XY: 1 AN XY: 67210

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

African (AFR) AF: 0.00 AC: 0 AN: 38058

American (AMR) AF: 0.00 AC: 0 AN: 13990

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3312

East Asian (EAS) AF: 0.00 AC: 0 AN: 4818

South Asian (SAS) AF: 0.00 AC: 0 AN: 4402

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 7614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.0000470 AC: 3 AN: 63896

Other (OTH) AF: 0.00 AC: 0 AN: 1896

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.27

Splicing

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

Other links and lift over

dbSNP: rs34571703; hg19: chr10-101949591;