9-740769-CTTTTTTTTTTT-CTTTTTTTTTTTT

Position:

• chr9-740769-CTTTTTTTTTTT-CTTTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_015158.5(KANK1):​c.3554-5dup variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0096 (13 hom., cov: 0)
  • Exomes 𝑓: 0.022 (3 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.110

Genes affected

KANK1 (HGNC:19309): (KN motif and ankyrin repeat domains 1) The protein encoded by this gene belongs to the Kank family of proteins, which contain multiple ankyrin repeat domains. This family member functions in cytoskeleton formation by regulating actin polymerization. This gene is a candidate tumor suppressor for renal cell carcinoma. Mutations in this gene cause cerebral palsy spastic quadriplegic type 2, a central nervous system development disorder. A t(5;9) translocation results in fusion of the platelet-derived growth factor receptor beta gene (PDGFRB) on chromosome 5 with this gene in a myeloproliferative neoplasm featuring severe thrombocythemia. Alternative splicing of this gene results in multiple transcript variants. A related pseudogene has been identified on chromosome 20. [provided by RefSeq, Dec 2014]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00958 (1387/144724) while in subpopulation EAS AF= 0.0408 (196/4808). AF 95% confidence interval is 0.0361. There are 13 homozygotes in gnomad4. There are 765 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1387 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-5dup		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.3554-5dup		intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.00960 AC: 1389 AN: 144678 Hom.: 13 Cov.: 0

Gnomad AFR AF: 0.00969

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0116

Gnomad ASJ AF: 0.00272

Gnomad EAS AF: 0.0409

Gnomad SAS AF: 0.00674

Gnomad FIN AF: 0.0288

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.00491

Gnomad OTH AF: 0.00802

GnomAD4 exome AF: 0.0219 AC: 29574 AN: 1349242 Hom.: 3 Cov.: 0 AF XY: 0.0215 AC XY: 14433 AN XY: 670646

Gnomad4 AFR exome AF: 0.0224

Gnomad4 AMR exome AF: 0.0334

Gnomad4 ASJ exome AF: 0.0265

Gnomad4 EAS exome AF: 0.0498

Gnomad4 SAS exome AF: 0.0200

Gnomad4 FIN exome AF: 0.0224

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0248

GnomAD4 genome AF: 0.00958 AC: 1387 AN: 144724 Hom.: 13 Cov.: 0 AF XY: 0.0109 AC XY: 765 AN XY: 70086

Gnomad4 AFR AF: 0.00969

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00272

Gnomad4 EAS AF: 0.0408

Gnomad4 SAS AF: 0.00654

Gnomad4 FIN AF: 0.0288

Gnomad4 NFE AF: 0.00491

Gnomad4 OTH AF: 0.00749

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs58169581; hg19: chr9-740769;