Genetic Variant KANK1:c.-362+25070G>A (chr9-498343-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000382303.5(KANK1):c.-362+25070G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00763 in 152,236 control chromosomes in the GnomAD database, including 17 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 0.0076 ( 17 hom., cov: 32)

Consequence

KANK1
ENST00000382303.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.82

Publications

0 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.97).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00763 (1161/152236) while in subpopulation AFR AF = 0.0253 (1050/41520). AF 95% confidence interval is 0.024. There are 17 homozygotes in GnomAd4. There are 560 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 17 Unknown,AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	Protein	UniProt
KANK1	NM_001256876.3 link	c.-362+25070G>A	intron_variant	Intron 3 of 15	NP_001243805.1	Q14678-1
KANK1	XM_047423040.1 link	c.-84+25070G>A	intron_variant	Intron 2 of 12	XP_047278996.1
KANK1	XM_047423041.1 link	c.-566+25070G>A	intron_variant	Intron 2 of 16	XP_047278997.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382303.5 link	c.-362+25070G>A		intron_variant	Intron 3 of 15	1		ENSP00000371740.1		Q14678-1
KANK1	ENST00000688973.1 link	n.405+25070G>A		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes

AF:

0.00761

AC:

1157

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0253

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00347

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00334

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

GnomAD4 genome

AF:

0.00763

AC:

1161

AN:

152236

Hom.:

Cov.:

AF XY:

0.00752

AC XY:

560

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0253

AC:

1050

AN:

41520

American (AMR)

AF:

0.00346

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000691

AC:

AN:

68034

Other (OTH)

AF:

0.00331

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

129

194

258

323

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:

0.00219

Hom.:

Bravo

AF:

0.00859

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.97

CADD

Benign

0.063

(source)

DANN

Benign

0.73

PhyloP100

-2.8

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over