9-677089-G-A

Position:

• chr9-677089-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_015158.5(KANK1):​c.37+80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00361 in 1,281,958 control chromosomes in the GnomAD database, including 140 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.017 (81 hom., cov: 33)
  • Exomes 𝑓: 0.0019 (59 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.718

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-677089-G-A is Benign according to our data. Variant chr9-677089-G-A is described in ClinVar as [Benign]. Clinvar id is 1242096.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK1	NM_015158.5	c.37+80G>A		intron_variant		ENST00000382297.7	NP_055973.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK1	ENST00000382297.7	c.37+80G>A		intron_variant		1	NM_015158.5	ENSP00000371734	P2
	ENST00000421645.2	n.219-2710C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0166 AC: 2520 AN: 152052 Hom.: 81 Cov.: 33

Gnomad AFR AF: 0.0572

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00701

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00187 AC: 2108 AN: 1129788 Hom.: 59 AF XY: 0.00159 AC XY: 904 AN XY: 570014

Gnomad4 AFR exome AF: 0.0615

Gnomad4 AMR exome AF: 0.00312

Gnomad4 ASJ exome AF: 0.0000866

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000191

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000214

Gnomad4 OTH exome AF: 0.00399

GnomAD4 genome AF: 0.0166 AC: 2521 AN: 152170 Hom.: 81 Cov.: 33 AF XY: 0.0159 AC XY: 1183 AN XY: 74386

Gnomad4 AFR AF: 0.0571

Gnomad4 AMR AF: 0.00700

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.0132

Alfa AF: 0.0123 Hom.: 8

Bravo AF: 0.0194

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 25, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	8.0
DANN	Benign	0.67

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

LitVar

Other links and lift over

dbSNP: rs75543046; hg19: chr9-677089;