Variant 19-11170023-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001136191.3(KANK2):c.2412+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0189 in 1,611,970 control chromosomes in the GnomAD database, including 359 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 19 hom., cov: 32)

Exomes 𝑓: 0.020 ( 340 hom. )

Consequence

KANK2
NM_001136191.3 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.777

Variant links:

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 links:

KANK2 (HGNC:):

KANK2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 19-11170023-G-A is Benign according to our data. Variant chr19-11170023-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1316937.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0122 (1859/152306) while in subpopulation SAS AF= 0.0244 (118/4830). AF 95% confidence interval is 0.0209. There are 19 homozygotes in gnomad4. There are 853 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KANK2	NM_001136191.3 linkuse as main transcript	c.2412+25C>T		intron_variant		ENST00000586659.6	NP_001129663.1	Q63ZY3-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KANK2	ENST00000586659.6 linkuse as main transcript	c.2412+25C>T		intron_variant		1	NM_001136191.3	ENSP00000465650.1		Q63ZY3-1

Frequencies

GnomAD3 genomes

AF:

0.0122

AC:

1854

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00398

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00740

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.0123

Gnomad SAS

AF:

0.0246

Gnomad FIN

AF:

0.00490

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0190

Gnomad OTH

AF:

0.00907

GnomAD3 exomes

AF:

0.0149

AC:

3744

AN:

250922

Hom.:

AF XY:

0.0163

AC XY:

2214

AN XY:

135590

show subpopulations

Gnomad AFR exome

AF:

0.00388

Gnomad AMR exome

AF:

0.00697

Gnomad ASJ exome

AF:

0.0116

Gnomad EAS exome

AF:

0.0122

Gnomad SAS exome

AF:

0.0258

Gnomad FIN exome

AF:

0.00738

Gnomad NFE exome

AF:

0.0182

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0196

AC:

28634

AN:

1459664

Hom.:

340

Cov.:

AF XY:

0.0197

AC XY:

14261

AN XY:

725694

show subpopulations

Gnomad4 AFR exome

AF:

0.00308

Gnomad4 AMR exome

AF:

0.00694

Gnomad4 ASJ exome

AF:

0.0109

Gnomad4 EAS exome

AF:

0.0105

Gnomad4 SAS exome

AF:

0.0248

Gnomad4 FIN exome

AF:

0.00772

Gnomad4 NFE exome

AF:

0.0214

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.0122

AC:

1859

AN:

152306

Hom.:

Cov.:

AF XY:

0.0115

AC XY:

853

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00397

Gnomad4 AMR

AF:

0.00739

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.0124

Gnomad4 SAS

AF:

0.0244

Gnomad4 FIN

AF:

0.00490

Gnomad4 NFE

AF:

0.0190

Gnomad4 OTH

AF:

0.0113

Alfa

AF:

0.0138

Hom.:

Bravo

AF:

0.0121

Asia WGS

AF:

0.0230

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 20, 2020	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.32

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over