chr16-84313001-G-A

Position:

chr16-84313001-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_021197.4(WFDC1):c.185G>A(p.Arg62Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,264,144 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00022 ( 0 hom. )

Consequence

WFDC1
NM_021197.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.125

Variant links:

Genes affected

WFDC1 (HGNC:15466): (WAP four-disulfide core domain 1) This gene encodes a member of the WAP-type four disulfide core domain family. The WAP-type four-disulfide core domain 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 mapped to chromosome 16q24, an area of frequent loss of heterozygosity in cancers, including prostate, breast and hepatocellular cancers and Wilms' tumor. This gene is downregulated in many cancer types and may be involved in the inhibition of cell proliferation. The encoded protein may also play a role in the susceptibility of certain CD4 memory T cells to human immunodeficiency virus infection. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2013]

WFDC1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12593168).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WFDC1	NM_021197.4 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/7	ENST00000219454.10	NP_067020.2	Q9HC57
WFDC1	NM_001282466.2 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/7		NP_001269395.1	Q9HC57
WFDC1	NM_001282467.2 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/7		NP_001269396.1	Q9HC57
WFDC1	XM_047434411.1 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/6		XP_047290367.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WFDC1	ENST00000219454.10 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/7	1	NM_021197.4	ENSP00000219454.5		Q9HC57
WFDC1	ENST00000568638.1 linkuse as main transcript	c.185G>A	p.Arg62Gln	missense_variant	2/7	2		ENSP00000456920.1		Q9HC57

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151502

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000221

AC:

246

AN:

1112642

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

113

AN XY:

534256

show subpopulations

Gnomad4 AFR exome

AF:

0.0000452

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000592

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000253

Gnomad4 OTH exome

AF:

0.000137

GnomAD4 genome

AF:

0.000112

AC:

AN:

151502

Hom.:

Cov.:

AF XY:

0.0000946

AC XY:

AN XY:

74004

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.000106

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

Aug 28, 2024

The c.185G>A (p.R62Q) alteration is located in exon 2 (coding exon 2) of the WFDC1 gene. This alteration results from a G to A substitution at nucleotide position 185, causing the arginine (R) at amino acid position 62 to be replaced by a glutamine (Q). 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

0.14

BayesDel_addAF

Benign

-0.091

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.028

LIST_S2

Benign

0.65

.;T

M_CAP

Uncertain

0.24

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.48

N;N

REVEL

Benign

0.18

Sift

Benign

0.28

T;T

Sift4G

Benign

0.14

T;T

Polyphen

0.68

P;P

Vest4

0.093

MutPred

0.39

Gain of glycosylation at P67 (P = 0.1576);Gain of glycosylation at P67 (P = 0.1576);

MVP

0.45

MPC

0.036

ClinPred

0.23

GERP RS

0.38

Varity_R

0.038

gMVP

0.48

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