chr9-740769-CTTTTT-C

Variant names:

• chr9-740769-CTTTTT-C
• rs58169581
• NM_015158.5:c.3554-9_3554-5delTTTTT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_015158.5(KANK1):​c.3554-9_3554-5delTTTTT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00754 in 1,472,042 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0013 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0082 (0 hom.)
• Consequence: KANK1 NM_015158.5 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.735

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 -6 ACMG points.

• BP6: Variant 9-740769-CTTTTT-C is Benign according to our data. Variant chr9-740769-CTTTTT-C is described in ClinVar as [Benign]. Clinvar id is 931793.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd4 at 190 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.3554-9_3554-5delTTTTT		splice_region_variant, intron_variant	Intron 8 of 11	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.3554-22_3554-18delTTTTT		intron_variant	Intron 8 of 11	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.00131 AC: 190 AN: 144682 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00151

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000702

Gnomad ASJ AF: 0.000302

Gnomad EAS AF: 0.000207

Gnomad SAS AF: 0.000435

Gnomad FIN AF: 0.00274

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00152

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00822 AC: 10908 AN: 1327314 Hom.: 0 AF XY: 0.00821 AC XY: 5413 AN XY: 659696

Gnomad4 AFR exome AF: 0.00776

Gnomad4 AMR exome AF: 0.00332

Gnomad4 ASJ exome AF: 0.00250

Gnomad4 EAS exome AF: 0.00130

Gnomad4 SAS exome AF: 0.00890

Gnomad4 FIN exome AF: 0.00667

Gnomad4 NFE exome AF: 0.00888

Gnomad4 OTH exome AF: 0.00695

GnomAD4 genome AF: 0.00131 AC: 190 AN: 144728 Hom.: 0 Cov.: 0 AF XY: 0.00140 AC XY: 98 AN XY: 70096

Gnomad4 AFR AF: 0.00151

Gnomad4 AMR AF: 0.0000701

Gnomad4 ASJ AF: 0.000302

Gnomad4 EAS AF: 0.000208

Gnomad4 SAS AF: 0.000436

Gnomad4 FIN AF: 0.00274

Gnomad4 NFE AF: 0.00152

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Cerebral palsy, spastic quadriplegic, 2 Benign:1

Sep 26, 2018

Centre for Mendelian Genomics, University Medical Centre Ljubljana

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2. -

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;