chr9-699065-C-G

Variant names:

• chr9-699065-C-G
• rs10975882
• NM_015158.5:c.38-11739C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015158.5(KANK1):​c.38-11739C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.351 in 152,034 control chromosomes in the GnomAD database, including 10,695 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (10695 hom., cov: 32)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.163
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KANK1	NM_015158.5	c.38-11739C>G		intron_variant	Intron 2 of 11	ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.38-11739C>G		intron_variant	Intron 2 of 11	1	NM_015158.5	ENSP00000371734.2

Frequencies

GnomAD3 genomes AF: 0.351 AC: 53380 AN: 151916 Hom.: 10695 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.359

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.469

Gnomad FIN AF: 0.384

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.464

Gnomad OTH AF: 0.375

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.351 AC: 53384 AN: 152034 Hom.: 10695 Cov.: 32 AF XY: 0.348 AC XY: 25865 AN XY: 74316

African (AFR) AF: 0.193 AC: 8006 AN: 41486

American (AMR) AF: 0.268 AC: 4095 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.488 AC: 1694 AN: 3472

East Asian (EAS) AF: 0.0950 AC: 490 AN: 5156

South Asian (SAS) AF: 0.469 AC: 2255 AN: 4810

European-Finnish (FIN) AF: 0.384 AC: 4049 AN: 10558

Middle Eastern (MID) AF: 0.412 AC: 121 AN: 294

European-Non Finnish (NFE) AF: 0.464 AC: 31566 AN: 67960

Other (OTH) AF: 0.371 AC: 783 AN: 2112

Alfa AF: 0.417 Hom.: 1978

Bravo AF: 0.331

Asia WGS AF: 0.223 AC: 781 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.4
DANN	Benign	0.71
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs10975882; hg19: chr9-699065;