9-676837-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_015158.5(KANK1):c.-83-53_-83-52insG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.432 in 679,772 control chromosomes in the GnomAD database, including 68,608 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.51 (21478 hom., cov: 0)
  • Exomes 𝑓: 0.41 (47130 hom.)
• Consequence: KANK1 NM_015158.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.479

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 -10 ACMG points.

• BP6: Variant 9-676837-T-TG is Benign according to our data. Variant chr9-676837-T-TG is described in ClinVar as [Benign]. Clinvar id is 1228050.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.726 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KANK1	NM_015158.5	c.-83-53_-83-52insG		intron_variant		ENST00000382297.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KANK1	ENST00000382297.7	c.-83-53_-83-52insG		intron_variant		1	NM_015158.5	P2
	ENST00000421645.2	n.219-2459_219-2458insC		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.507 AC: 76968 AN: 151794 Hom.: 21426 Cov.: 0

Gnomad AFR AF: 0.733

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.554

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.472

Gnomad MID AF: 0.465

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.463

GnomAD4 exome AF: 0.410 AC: 216274 AN: 527860 Hom.: 47130 AF XY: 0.402 AC XY: 113663 AN XY: 282576

Gnomad4 AFR exome AF: 0.735

Gnomad4 AMR exome AF: 0.601

Gnomad4 ASJ exome AF: 0.386

Gnomad4 EAS exome AF: 0.567

Gnomad4 SAS exome AF: 0.328

Gnomad4 FIN exome AF: 0.451

Gnomad4 NFE exome AF: 0.370

Gnomad4 OTH exome AF: 0.423

GnomAD4 genome AF: 0.507 AC: 77077 AN: 151912 Hom.: 21478 Cov.: 0 AF XY: 0.509 AC XY: 37769 AN XY: 74258

Gnomad4 AFR AF: 0.733

Gnomad4 AMR AF: 0.554

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.579

Gnomad4 SAS AF: 0.335

Gnomad4 FIN AF: 0.472

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.468

Alfa AF: 0.458 Hom.: 2137

Bravo AF: 0.526

Asia WGS AF: 0.525 AC: 1825 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs3831027; hg19: chr9-676837;