rs4804149

Variant names:

• chr19-11173352-T-C
• rs4804149
• NM_001136191.3:c.2069-229A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001136191.3(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 NM_001136191.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• wooly hair-palmoplantar keratoderma syndrome

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae)
• nephrotic syndrome 16

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
KANK2	NM_001136191.3	c.2069-229A>G		intron_variant	Intron 9 of 12	ENST00000586659.6	NP_001129663.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KANK2	ENST00000586659.6	c.2069-229A>G		intron_variant	Intron 9 of 12	1	NM_001136191.3	ENSP00000465650.1
KANK2	ENST00000589359.5	c.2093-229A>G		intron_variant	Intron 9 of 12	5		ENSP00000468002.1
KANK2	ENST00000589894.1	c.2069-229A>G		intron_variant	Intron 7 of 9	5		ENSP00000467029.1
KANK2	ENST00000588787.5	c.266-229A>G		intron_variant	Intron 2 of 4	5		ENSP00000464896.1

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

African (AFR) AF: 0.389 AC: 16103 AN: 41436

American (AMR) AF: 0.375 AC: 5719 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 602 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1273 AN: 5174

South Asian (SAS) AF: 0.157 AC: 754 AN: 4812

European-Finnish (FIN) AF: 0.279 AC: 2948 AN: 10570

Middle Eastern (MID) AF: 0.204 AC: 60 AN: 294

European-Non Finnish (NFE) AF: 0.282 AC: 19135 AN: 67954

Other (OTH) AF: 0.308 AC: 652 AN: 2114

Alfa AF: 0.288 Hom.: 11694

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

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	4.1
DANN	Benign	0.63
PhyloP100		-0.047
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4804149; hg19: chr19-11284028;