9-730266-C-T

Variant names:

• chr9-730266-C-T
• rs113240136
• NM_015158.5:c.2896+18C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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

ACMG classification

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	NM_015158.5	MANE Select	c.2896+18C>T		intron	N/A	NP_055973.2
	KANK1	NM_001256876.3		c.2896+18C>T		intron	N/A	NP_001243805.1
	KANK1	NM_001256877.3		c.2896+18C>T		intron	N/A	NP_001243806.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	ENST00000382297.7	TSL:1 MANE Select	c.2896+18C>T		intron	N/A	ENSP00000371734.2
	KANK1	ENST00000382303.5	TSL:1	c.2896+18C>T		intron	N/A	ENSP00000371740.1
	KANK1	ENST00000382293.7	TSL:1	c.2422+18C>T		intron	N/A	ENSP00000371730.3

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

GnomAD2 exomes AF: 0.00648 AC: 1626 AN: 250804 AF XY: 0.00680

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.: 29 AF XY: 0.00996 AC XY: 7231 AN XY: 726260

African (AFR) AF: 0.00123 AC: 41 AN: 33420

American (AMR) AF: 0.00210 AC: 94 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00299 AC: 78 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 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: 13 AN: 5762

European-Non Finnish (NFE) AF: 0.0120 AC: 13265 AN: 1109910

Other (OTH) AF: 0.00814 AC: 491 AN: 60318

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

African (AFR) AF: 0.00156 AC: 65 AN: 41564

American (AMR) AF: 0.00216 AC: 33 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00269 AC: 13 AN: 4824

European-Finnish (FIN) AF: 0.00527 AC: 56 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0105 AC: 713 AN: 68032

Other (OTH) AF: 0.00378 AC: 8 AN: 2114

Alfa AF: 0.00881 Hom.: 11

Bravo AF: 0.00526

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.1
DANN	Benign	0.96
PhyloP100		0.20
Mutation Taster		=100/0	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: rs113240136; hg19: chr9-730266;