Variant chr17-50836029-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_175575.6(WFIKKN2):c.92G>A(p.Arg31Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0102 in 1,601,110 control chromosomes in the GnomAD database, including 114 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0078 ( 6 hom., cov: 33)

Exomes 𝑓: 0.011 ( 108 hom. )

Consequence

WFIKKN2
NM_175575.6 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0340

Variant links:

Genes affected

WFIKKN2 (HGNC:30916): (WAP, follistatin/kazal, immunoglobulin, kunitz and netrin domain containing 2) The WFIKKN1 protein contains a WAP domain, follistatin domain, immunoglobulin domain, two tandem Kunitz domains, and an NTR domain. This gene encodes a WFIKKN1-related protein which has the same domain organization as the WFIKKN1 protein. The WAP-type, follistatin type, Kunitz-type, and NTR-type protease inhibitory domains may control the action of multiple types of proteases. [provided by RefSeq, Jul 2008]

WFIKKN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035322309).

BP6

Variant 17-50836029-G-A is Benign according to our data. Variant chr17-50836029-G-A is described in ClinVar as [Benign]. Clinvar id is 775327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFIKKN2	NM_175575.6 linkuse as main transcript	c.92G>A	p.Arg31Gln	missense_variant	1/2	ENST00000311378.5	NP_783165.1	Q8TEU8
WFIKKN2	NM_001330341.2 linkuse as main transcript	c.-70+997G>A		intron_variant			NP_001317270.1	Q8TEU8C9J6G4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFIKKN2	ENST00000311378.5 linkuse as main transcript	c.92G>A	p.Arg31Gln	missense_variant	1/2	1	NM_175575.6	ENSP00000311184.4		Q8TEU8
WFIKKN2	ENST00000426127.1 linkuse as main transcript	c.-70+997G>A		intron_variant		2		ENSP00000405889.1		C9J6G4

Frequencies

GnomAD3 genomes

AF:

0.00777

AC:

1183

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.0669

Gnomad AMR

AF:

0.00451

Gnomad ASJ

AF:

0.00115

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.00386

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00621

GnomAD3 exomes

AF:

0.00674

AC:

1488

AN:

220752

Hom.:

AF XY:

0.00683

AC XY:

821

AN XY:

120222

show subpopulations

Gnomad AFR exome

AF:

0.00166

Gnomad AMR exome

AF:

0.00411

Gnomad ASJ exome

AF:

0.00127

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00247

Gnomad FIN exome

AF:

0.00431

Gnomad NFE exome

AF:

0.0117

Gnomad OTH exome

AF:

0.00601

GnomAD4 exome

AF:

0.0105

AC:

15218

AN:

1448752

Hom.:

108

Cov.:

AF XY:

0.0103

AC XY:

7427

AN XY:

719800

show subpopulations

Gnomad4 AFR exome

AF:

0.00177

Gnomad4 AMR exome

AF:

0.00465

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00239

Gnomad4 FIN exome

AF:

0.00419

Gnomad4 NFE exome

AF:

0.0127

Gnomad4 OTH exome

AF:

0.00797

GnomAD4 genome

AF:

0.00775

AC:

1181

AN:

152358

Hom.:

Cov.:

AF XY:

0.00744

AC XY:

554

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.00293

Gnomad4 AMR

AF:

0.00451

Gnomad4 ASJ

AF:

0.00115

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00386

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00614

Alfa

AF:

0.0114

Hom.:

Bravo

AF:

0.00751

TwinsUK

AF:

0.0129

AC:

ALSPAC

AF:

0.0127

AC:

ESP6500AA

AF:

0.00205

AC:

ESP6500EA

AF:

0.0109

AC:

ExAC

AF:

0.00607

AC:

734

Asia WGS

AF:

0.00231

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.081

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

CADD

Benign

1.4

DANN

Benign

0.93

DEOGEN2

Benign

0.011

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.064

LIST_S2

Benign

0.49

MetaRNN

Benign

0.0035

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.26

PROVEAN

Benign

-0.010

REVEL

Benign

0.10

Sift

Benign

0.65

Sift4G

Benign

0.62

Polyphen

0.0

Vest4

0.055

MVP

0.27

MPC

0.19

ClinPred

0.0014

GERP RS

-3.1

Varity_R

0.023

gMVP

0.27

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

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