rs3831027

Variant names:

• chr9-676837-T-TG
• rs3831027
• NM_015158.5:c.-83-53_-83-52insG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015158.5(KANK1):​c.-83-53_-83-52insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 679,772 control chromosomes in the GnomAD database, including 68,608 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (21478 hom., cov: 0)
  • Exomes 𝑓: 0.41 (47130 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.479
• Publications: 2 publications found

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]

KANK1 Gene-Disease associations (from GenCC):

• spastic quadriplegic cerebral palsy

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• cerebral palsy, spastic quadriplegic, 2

  Inheritance: Unknown, AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

ENSG00000227914 (HGNC:58139):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 9-676837-T-TG is Benign according to our data. Variant chr9-676837-T-TG is described in ClinVar as [Benign]. Clinvar id is 1228050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.-83-53_-83-52insG		intron_variant	Intron 1 of 11	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-53_-83-52insG		intron_variant	Intron 1 of 11	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76968 AN: 151794 Hom.: 21426 Cov.: 0

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.410 AC: 216274 AN: 527860 Hom.: 47130 AF XY: 0.402 AC XY: 113663 AN XY: 282576

African (AFR) AF: 0.735 AC: 9995 AN: 13600

American (AMR) AF: 0.601 AC: 15591 AN: 25962

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 5890 AN: 15250

East Asian (EAS) AF: 0.567 AC: 18574 AN: 32758

South Asian (SAS) AF: 0.328 AC: 16787 AN: 51168

European-Finnish (FIN) AF: 0.451 AC: 21173 AN: 46968

Middle Eastern (MID) AF: 0.413 AC: 1500 AN: 3632

European-Non Finnish (NFE) AF: 0.370 AC: 114975 AN: 310624

Other (OTH) AF: 0.423 AC: 11789 AN: 27898

GnomAD4 genome AF: 0.507 AC: 77077 AN: 151912 Hom.: 21478 Cov.: 0 AF XY: 0.509 AC XY: 37769 AN XY: 74258

African (AFR) AF: 0.733 AC: 30377 AN: 41426

American (AMR) AF: 0.554 AC: 8463 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.402 AC: 1390 AN: 3462

East Asian (EAS) AF: 0.579 AC: 2987 AN: 5160

South Asian (SAS) AF: 0.335 AC: 1613 AN: 4810

European-Finnish (FIN) AF: 0.472 AC: 4971 AN: 10542

Middle Eastern (MID) AF: 0.469 AC: 138 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25744 AN: 67934

Other (OTH) AF: 0.468 AC: 989 AN: 2112

Alfa AF: 0.458 Hom.: 2137

Bravo AF: 0.526

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.48
Mutation Taster		=67/33	polymorphism

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

Other links and lift over

dbSNP: rs3831027; hg19: chr9-676837;