Variant 17-50836025-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_175575.6(WFIKKN2):c.88C>T(p.Pro30Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000069 in 1,449,066 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

WFIKKN2
NM_175575.6 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.694

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 Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.054565072).

BP6

Variant 17-50836025-C-T is Benign according to our data. Variant chr17-50836025-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 3190511.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFIKKN2	NM_175575.6 linkuse as main transcript	c.88C>T	p.Pro30Ser	missense_variant	1/2	ENST00000311378.5	NP_783165.1	Q8TEU8
WFIKKN2	NM_001330341.2 linkuse as main transcript	c.-70+993C>T		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.88C>T	p.Pro30Ser	missense_variant	1/2	1	NM_175575.6	ENSP00000311184.4		Q8TEU8
WFIKKN2	ENST00000426127.1 linkuse as main transcript	c.-70+993C>T		intron_variant		2		ENSP00000405889.1		C9J6G4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.90e-7

AC:

AN:

1449066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719970

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.04e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 12, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

0.52

DANN

Benign

0.74

DEOGEN2

Benign

0.013

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.38

M_CAP

Benign

0.023

MetaRNN

Benign

0.055

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.31

PROVEAN

Benign

0.49

REVEL

Benign

0.14

Sift

Benign

0.26

Sift4G

Benign

0.41

Polyphen

0.0

Vest4

0.058

MutPred

0.49

Loss of catalytic residue at P29 (P = 0.0151);

MVP

0.14

MPC

0.17

ClinPred

0.70

GERP RS

1.0

Varity_R

0.019

gMVP

0.30

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over