Genetic Variant KANK1:c.2896+18C>T (chr9-730266-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

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

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.199

Publications

1 publications found

Variant links:

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

KANK1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 445945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 3 Unknown,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5 link	c.2896+18C>T		intron_variant	Intron 4 of 11	ENST00000382297.7	NP_055973.2	Q14678-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7 link	c.2896+18C>T		intron_variant	Intron 4 of 11	1	NM_015158.5	ENSP00000371734.2		Q14678-1

Frequencies

GnomAD3 genomes

AF:

0.00595

AC:

906

AN:

152196

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.00648

AC:

1626

AN:

250804

AF XY:

0.00680

show subpopulations

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 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.:

AF XY:

0.00996

AC XY:

7231

AN XY:

726260

show subpopulations

African (AFR)

AF:

0.00123

AC:

AN:

33420

American (AMR)

AF:

0.00210

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00299

AC:

AN:

26128

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00443

AC:

382

AN:

86202

European-Finnish (FIN)

AF:

0.00614

AC:

328

AN:

53414

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0120

AC:

13265

AN:

1109910

Other (OTH)

AF:

0.00814

AC:

491

AN:

60318

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.485

Heterozygous variant carriers

712

1424

2136

2848

3560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

502

1004

1506

2008

2510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00595

AC:

906

AN:

152314

Hom.:

Cov.:

AF XY:

0.00541

AC XY:

403

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.00156

AC:

AN:

41564

American (AMR)

AF:

0.00216

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00269

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00527

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0105

AC:

713

AN:

68032

Other (OTH)

AF:

0.00378

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00881

Hom.:

Bravo

AF:

0.00526

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2020

GeneDx

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 24, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

7.1

(source)

DANN

Benign

0.96

PhyloP100

0.20

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over