chr9-740769-CTTTTTTTT-C

Position:

• chr9-740769-CTTTTTTTT-C

Variant summary

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

The NM_015158.5(KANK1):​c.3554-12_3554-5del variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000192 in 1,503,922 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 0.000014 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00021 (0 hom.)
• Consequence: KANK1 NM_015158.5 splice_polypyrimidine_tract, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.56

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 GnomAdExome4 at 287 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-12_3554-5del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.3554-12_3554-5del		splice_polypyrimidine_tract_variant, intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.0000138 AC: 2 AN: 144716 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000252

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: 0.0000152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000211 AC: 287 AN: 1359206 Hom.: 0 AF XY: 0.000241 AC XY: 163 AN XY: 675622

Gnomad4 AFR exome AF: 0.00117

Gnomad4 AMR exome AF: 0.000119

Gnomad4 ASJ exome AF: 0.0000855

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00131

Gnomad4 FIN exome AF: 0.000367

Gnomad4 NFE exome AF: 0.000119

Gnomad4 OTH exome AF: 0.0000714

GnomAD4 genome AF: 0.0000138 AC: 2 AN: 144716 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 70042

Gnomad4 AFR AF: 0.0000252

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000152

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;