rs113240136

Positions:

• chr9-730266-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_015158.5(KANK1):​c.2896+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00968 in 1,611,880 control chromosomes in the GnomAD database, including 110 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0059 (3 hom., cov: 33)
  • Exomes 𝑓: 0.010 (107 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.199

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 9-730266-C-T is Benign according to our data. Variant chr9-730266-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 445945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 906 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.2896+18C>T		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.2896+18C>T		intron_variant		1	NM_015158.5	ENSP00000371734	P2

Frequencies

GnomAD3 genomes AF: 0.00595 AC: 906 AN: 152196 Hom.: 3 Cov.: 33

Gnomad AFR AF: 0.00157

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00269

Gnomad FIN AF: 0.00527

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0105

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00648 AC: 1626 AN: 250804 Hom.: 12 AF XY: 0.00680 AC XY: 923 AN XY: 135692

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.00214

Gnomad ASJ exome AF: 0.00328

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00474

Gnomad FIN exome AF: 0.00596

Gnomad NFE exome AF: 0.0105

Gnomad OTH exome AF: 0.00685

GnomAD4 exome AF: 0.0101 AC: 14692 AN: 1459566 Hom.: 107 Cov.: 29 AF XY: 0.00996 AC XY: 7231 AN XY: 726260

Gnomad4 AFR exome AF: 0.00123

Gnomad4 AMR exome AF: 0.00210

Gnomad4 ASJ exome AF: 0.00299

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00443

Gnomad4 FIN exome AF: 0.00614

Gnomad4 NFE exome AF: 0.0120

Gnomad4 OTH exome AF: 0.00814

GnomAD4 genome AF: 0.00595 AC: 906 AN: 152314 Hom.: 3 Cov.: 33 AF XY: 0.00541 AC XY: 403 AN XY: 74482

Gnomad4 AFR AF: 0.00156

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00269

Gnomad4 FIN AF: 0.00527

Gnomad4 NFE AF: 0.0105

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00986 Hom.: 9

Bravo AF: 0.00526

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Aug 24, 2017	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.96

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: rs113240136; hg19: chr9-730266;