chr9-740769-CT-C

Position:

• chr9-740769-CT-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015158.5(KANK1):​c.3554-5del variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0021 (0 hom., cov: 0)
  • Exomes 𝑓: 0.12 (0 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 9-740769-CT-C is Benign according to our data. Variant chr9-740769-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 1316657.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.241 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.00206 AC: 298 AN: 144648 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00257

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00162

Gnomad ASJ AF: 0.000604

Gnomad EAS AF: 0.00456

Gnomad SAS AF: 0.000652

Gnomad FIN AF: 0.00604

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00132

Gnomad OTH AF: 0.00201

GnomAD4 exome AF: 0.116 AC: 147918 AN: 1274658 Hom.: 0 Cov.: 0 AF XY: 0.115 AC XY: 72715 AN XY: 634134

Gnomad4 AFR exome AF: 0.0654

Gnomad4 AMR exome AF: 0.158

Gnomad4 ASJ exome AF: 0.170

Gnomad4 EAS exome AF: 0.246

Gnomad4 SAS exome AF: 0.0795

Gnomad4 FIN exome AF: 0.0967

Gnomad4 NFE exome AF: 0.114

Gnomad4 OTH exome AF: 0.127

GnomAD4 genome AF: 0.00209 AC: 302 AN: 144692 Hom.: 0 Cov.: 0 AF XY: 0.00215 AC XY: 151 AN XY: 70074

Gnomad4 AFR AF: 0.00264

Gnomad4 AMR AF: 0.00168

Gnomad4 ASJ AF: 0.000604

Gnomad4 EAS AF: 0.00457

Gnomad4 SAS AF: 0.000654

Gnomad4 FIN AF: 0.00604

Gnomad4 NFE AF: 0.00132

Gnomad4 OTH AF: 0.00200

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 29, 2019

- -

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;