Variant 17-50836049-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_175575.6(WFIKKN2):c.112A>G(p.Ile38Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00242 in 1,604,616 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0017 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0025 ( 4 hom. )

Consequence

WFIKKN2
NM_175575.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058525503).

BS2

High Homozygotes in GnomAdExome4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFIKKN2	NM_175575.6 linkuse as main transcript	c.112A>G	p.Ile38Val	missense_variant	1/2	ENST00000311378.5	NP_783165.1	Q8TEU8
WFIKKN2	NM_001330341.2 linkuse as main transcript	c.-70+1017A>G		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.112A>G	p.Ile38Val	missense_variant	1/2	1	NM_175575.6	ENSP00000311184.4		Q8TEU8
WFIKKN2	ENST00000426127.1 linkuse as main transcript	c.-70+1017A>G		intron_variant		2		ENSP00000405889.1		C9J6G4

Frequencies

GnomAD3 genomes

AF:

0.00168

AC:

255

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00103

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00284

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00144

AC:

329

AN:

228606

Hom.:

AF XY:

0.00147

AC XY:

183

AN XY:

124158

show subpopulations

Gnomad AFR exome

AF:

0.000358

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00166

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000659

Gnomad FIN exome

AF:

0.000258

Gnomad NFE exome

AF:

0.00218

Gnomad OTH exome

AF:

0.00123

GnomAD4 exome

AF:

0.00250

AC:

3634

AN:

1452268

Hom.:

Cov.:

AF XY:

0.00246

AC XY:

1774

AN XY:

721640

show subpopulations

Gnomad4 AFR exome

AF:

0.000631

Gnomad4 AMR exome

AF:

0.00158

Gnomad4 ASJ exome

AF:

0.00166

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000778

Gnomad4 FIN exome

AF:

0.000363

Gnomad4 NFE exome

AF:

0.00298

Gnomad4 OTH exome

AF:

0.00200

GnomAD4 genome

AF:

0.00167

AC:

254

AN:

152348

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74516

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00282

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00264

Hom.:

Bravo

AF:

0.00168

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00415

AC:

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00279

AC:

ExAC

AF:

0.00115

AC:

139

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 26, 2022

The c.112A>G (p.I38V) alteration is located in exon 1 (coding exon 1) of the WFIKKN2 gene. This alteration results from a A to G substitution at nucleotide position 112, causing the isoleucine (I) at amino acid position 38 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.66

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.45

FATHMM_MKL

Benign

0.45

LIST_S2

Benign

0.55

M_CAP

Benign

0.0036

MetaRNN

Benign

0.0059

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.47

PROVEAN

Benign

0.060

REVEL

Benign

0.040

Sift

Benign

0.98

Sift4G

Benign

1.0

Polyphen

0.0010

Vest4

0.080

MVP

0.15

MPC

0.14

ClinPred

0.0091

GERP RS

1.7

Varity_R

0.038

gMVP

0.18

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