9-740769-CTTTTTTTTTTT-CTTTTTTTTTTTTTT

Position:

• chr9-740769-CTTTTTTTTTTT-CTTTTTTTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_015158.5(KANK1):​c.3554-7_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 0.000097 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000098 (0 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-7_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.3554-7_3554-5dup		intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.0000967 AC: 14 AN: 144718 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000277

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000211

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000985 AC: 134 AN: 1360858 Hom.: 0 Cov.: 0 AF XY: 0.000101 AC XY: 68 AN XY: 676540

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.000386

Gnomad4 ASJ exome AF: 0.000299

Gnomad4 EAS exome AF: 0.000264

Gnomad4 SAS exome AF: 0.0000780

Gnomad4 FIN exome AF: 0.000108

Gnomad4 NFE exome AF: 0.0000476

Gnomad4 OTH exome AF: 0.000143

GnomAD4 genome AF: 0.0000967 AC: 14 AN: 144764 Hom.: 0 Cov.: 0 AF XY: 0.0000998 AC XY: 7 AN XY: 70116

Gnomad4 AFR AF: 0.000277

Gnomad4 AMR AF: 0.000210

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;