Variant chr20-45469825-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006103.4(WFDC2):c.44T>A(p.Leu15His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,459,010 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WFDC2
NM_006103.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.612

Variant links:

Genes affected

WFDC2 (HGNC:15939): (WAP four-disulfide core domain 2) This gene encodes a protein that is a member of the WFDC domain family. The WFDC domain, or WAP Signature motif, contains eight cysteines forming four disulfide bonds at the core of the protein, and functions as a protease inhibitor in many family members. This gene is expressed in pulmonary epithelial cells, and was also found to be expressed in some ovarian cancers. The encoded protein is a small secretory protein, which may be involved in sperm maturation. [provided by RefSeq, Jul 2008]

WFDC2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WFDC2	NM_006103.4 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant	1/4	ENST00000372676.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WFDC2	ENST00000372676.8 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant	1/4	1	NM_006103.4	P1	Q14508-1
WFDC2	ENST00000217425.9 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant	1/3	1			Q14508-5
WFDC2	ENST00000339946.7 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant	1/3	1			Q14508-3
WFDC2	ENST00000447118.5 linkuse as main transcript	c.44T>A	p.Leu15His	missense_variant, NMD_transcript_variant	1/5	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000412

AC:

AN:

242564

Hom.:

AF XY:

0.00

AC XY:

AN XY:

131872

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000914

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1459010

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

725530

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:

0.00000540

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Apr 28, 2023

The c.44T>A (p.L15H) alteration is located in exon 1 (coding exon 1) of the WFDC2 gene. This alteration results from a T to A substitution at nucleotide position 44, causing the leucine (L) at amino acid position 15 to be replaced by a histidine (H). 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

Uncertain

0.38

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Benign

-0.19

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.41

T;.;.

Eigen

Benign

0.061

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.24

LIST_S2

Benign

0.46

T;T;T

M_CAP

Uncertain

0.24

MetaRNN

Uncertain

0.70

D;D;D

MetaSVM

Uncertain

-0.21

MutationAssessor

Benign

1.8

L;L;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.61

PROVEAN

Uncertain

-3.7

D;N;D

REVEL

Uncertain

0.33

Sift

Uncertain

0.0070

D;D;D

Sift4G

Uncertain

0.0020

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.56

MutPred

0.55

Gain of catalytic residue at L17 (P = 0.0726);Gain of catalytic residue at L17 (P = 0.0726);Gain of catalytic residue at L17 (P = 0.0726);

MVP

0.67

MPC

0.22

ClinPred

0.82

GERP RS

4.9

Varity_R

0.27

gMVP

0.73

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