19-11173352-T-C

Position:

• chr19-11173352-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000586659.6(KANK2):​c.2069-229A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.313 in 151,990 control chromosomes in the GnomAD database, including 7,782 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.31 (7782 hom., cov: 31)
• Consequence: KANK2 ENST00000586659.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 19-11173352-T-C is Benign according to our data. Variant chr19-11173352-T-C is described in ClinVar as [Benign]. Clinvar id is 1295441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.384 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK2	NM_001136191.3	c.2069-229A>G		intron_variant		ENST00000586659.6	NP_001129663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK2	ENST00000586659.6	c.2069-229A>G		intron_variant		1	NM_001136191.3	ENSP00000465650	P1
KANK2	ENST00000588787.5	c.267-229A>G		intron_variant		5		ENSP00000464896
KANK2	ENST00000589359.5	c.2093-229A>G		intron_variant		5		ENSP00000468002
KANK2	ENST00000589894.1	c.2069-229A>G		intron_variant		5		ENSP00000467029

Frequencies

GnomAD3 genomes AF: 0.313 AC: 47504 AN: 151872 Hom.: 7767 Cov.: 31

Gnomad AFR AF: 0.389

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.199

Gnomad NFE AF: 0.282

Gnomad OTH AF: 0.304

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

GnomAD4 genome AF: 0.313 AC: 47563 AN: 151990 Hom.: 7782 Cov.: 31 AF XY: 0.310 AC XY: 23064 AN XY: 74300

Gnomad4 AFR AF: 0.389

Gnomad4 AMR AF: 0.375

Gnomad4 ASJ AF: 0.173

Gnomad4 EAS AF: 0.246

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.282

Gnomad4 OTH AF: 0.308

Alfa AF: 0.284 Hom.: 8875

Bravo AF: 0.330

Asia WGS AF: 0.247 AC: 858 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 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.63

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: rs4804149; hg19: chr19-11284028;