19-11166719-G-GTGGCCCC

Position:

• chr19-11166719-G-GTGGCCCC

Variant summary

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

The NM_001136191.3(KANK2):​c.2503-115_2503-109dupGGGGCCA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.032 in 1,016,176 control chromosomes in the GnomAD database, including 991 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.035 (154 hom., cov: 31)
  • Exomes 𝑓: 0.031 (837 hom.)
• Consequence: KANK2 NM_001136191.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.76

Genes affected

KANK2 (HGNC:29300): (KN motif and ankyrin repeat domains 2) This gene encodes a member of the KN motif and ankyrin repeat domains (KANK) family of proteins, which play a role in cytoskeletal formation by regulating actin polymerization. The encoded protein functions in the sequestration of steroid receptor coactivators and possibly other proteins. Mutations in this gene are associated with impaired kidney podocyte function and nephrotic syndrome, and keratoderma and woolly hair. [provided by RefSeq, Jul 2016]

KANK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 19-11166719-G-GTGGCCCC is Benign according to our data. Variant chr19-11166719-G-GTGGCCCC is described in ClinVar as [Benign]. Clinvar id is 1273505.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.072 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK2	NM_001136191.3	c.2503-115_2503-109dupGGGGCCA		intron_variant		ENST00000586659.6	NP_001129663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK2	ENST00000586659.6	c.2503-115_2503-109dupGGGGCCA		intron_variant		1	NM_001136191.3	ENSP00000465650.1
KANK2	ENST00000589359.5	c.2527-115_2527-109dupGGGGCCA		intron_variant		5		ENSP00000468002.1
KANK2	ENST00000588787.5	c.610-115_610-109dupGGGGCCA		intron_variant		5		ENSP00000464896.1
KANK2	ENST00000587317.1	n.370-115_370-109dupGGGGCCA		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0354 AC: 5395 AN: 152198 Hom.: 153 Cov.: 31

Gnomad AFR AF: 0.00835

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.0756

Gnomad ASJ AF: 0.0170

Gnomad EAS AF: 0.00231

Gnomad SAS AF: 0.0275

Gnomad FIN AF: 0.0471

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0445

Gnomad OTH AF: 0.0320

GnomAD4 exome AF: 0.0314 AC: 27110 AN: 863860 Hom.: 837 AF XY: 0.0311 AC XY: 13956 AN XY: 448890

Gnomad4 AFR exome AF: 0.00702

Gnomad4 AMR exome AF: 0.0890

Gnomad4 ASJ exome AF: 0.0164

Gnomad4 EAS exome AF: 0.000836

Gnomad4 SAS exome AF: 0.0226

Gnomad4 FIN exome AF: 0.0471

Gnomad4 NFE exome AF: 0.0312

Gnomad4 OTH exome AF: 0.0290

GnomAD4 genome AF: 0.0354 AC: 5398 AN: 152316 Hom.: 154 Cov.: 31 AF XY: 0.0365 AC XY: 2721 AN XY: 74464

Gnomad4 AFR AF: 0.00832

Gnomad4 AMR AF: 0.0756

Gnomad4 ASJ AF: 0.0170

Gnomad4 EAS AF: 0.00231

Gnomad4 SAS AF: 0.0278

Gnomad4 FIN AF: 0.0471

Gnomad4 NFE AF: 0.0445

Gnomad4 OTH AF: 0.0317

Alfa AF: 0.0175 Hom.: 11

Bravo AF: 0.0353

Asia WGS AF: 0.0150 AC: 54 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

Jan 12, 2020

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs200597892; hg19: chr19-11277395;