9-555631-A-G

Variant names:

• chr9-555631-A-G
• rs2804311
• NM_015158.5:c.-84+50877A>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.-84+50877A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,080 control chromosomes in the GnomAD database, including 15,692 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 0.41 (15692 hom., cov: 33)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.366
• Publications: 3 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	NM_015158.5	MANE Select	c.-84+50877A>G		intron	N/A	NP_055973.2
	KANK1	NM_001256876.3		c.-84+14964A>G		intron	N/A	NP_001243805.1
	KANK1	NM_001256877.3		c.-84+5910A>G		intron	N/A	NP_001243806.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KANK1	ENST00000382297.7	TSL:1 MANE Select	c.-84+50877A>G		intron	N/A	ENSP00000371734.2
	KANK1	ENST00000382303.5	TSL:1	c.-84+14964A>G		intron	N/A	ENSP00000371740.1
	KANK1	ENST00000619269.5	TSL:5	c.-84+50877A>G		intron	N/A	ENSP00000477725.2

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62885 AN: 151962 Hom.: 15699 Cov.: 33

Gnomad AFR AF: 0.143

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.381

Gnomad ASJ AF: 0.472

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.594

Gnomad FIN AF: 0.505

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.567

Gnomad OTH AF: 0.442

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

GnomAD4 genome AF: 0.413 AC: 62870 AN: 152080 Hom.: 15692 Cov.: 33 AF XY: 0.413 AC XY: 30676 AN XY: 74338

African (AFR) AF: 0.143 AC: 5938 AN: 41516

American (AMR) AF: 0.381 AC: 5811 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.472 AC: 1638 AN: 3468

East Asian (EAS) AF: 0.235 AC: 1214 AN: 5172

South Asian (SAS) AF: 0.594 AC: 2861 AN: 4820

European-Finnish (FIN) AF: 0.505 AC: 5334 AN: 10560

Middle Eastern (MID) AF: 0.452 AC: 133 AN: 294

European-Non Finnish (NFE) AF: 0.567 AC: 38552 AN: 67954

Other (OTH) AF: 0.435 AC: 919 AN: 2112

Alfa AF: 0.523 Hom.: 11502

Bravo AF: 0.388

Asia WGS AF: 0.352 AC: 1225 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.59
DANN	Benign	0.67
PhyloP100		-0.37
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs2804311; hg19: chr9-555631;