dbSNP rs1991141067: WFDC2:p.Ala10Asp (chr20-45469810-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_006103.4(WFDC2):c.29C>A(p.Ala10Asp) 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 1,458,242 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A10V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WFDC2
NM_006103.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.652

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.21386603).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WFDC2	NM_006103.4 link	c.29C>A	p.Ala10Asp	missense_variant	Exon 1 of 4	ENST00000372676.8	NP_006094.3	Q14508-1A0A384MTN6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
WFDC2	ENST00000372676.8 link	c.29C>A	p.Ala10Asp	missense_variant	Exon 1 of 4	1	NM_006103.4	ENSP00000361761.3	Q14508-1
WFDC2	ENST00000217425.9 link	c.29C>A	p.Ala10Asp	missense_variant	Exon 1 of 3	1		ENSP00000217425.5	Q14508-5
WFDC2	ENST00000339946.7 link	c.29C>A	p.Ala10Asp	missense_variant	Exon 1 of 3	1		ENSP00000340215.3	Q14508-3
WFDC2	ENST00000447118.5 link	n.29C>A		non_coding_transcript_exon_variant	Exon 1 of 5	1		ENSP00000404760.1	A8K2M3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458242

Hom.:

Cov.:

AF XY:

0.00000552

AC XY:

AN XY:

725094

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:

0.00000360

Gnomad4 OTH exome

AF:

0.0000332

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.52

BayesDel_addAF

Benign

0.0013

BayesDel_noAF

Benign

-0.24

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.17

T;.;.

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.91

FATHMM_MKL

Benign

0.052

LIST_S2

Benign

0.41

T;T;T

M_CAP

Benign

0.074

MetaRNN

Benign

0.21

T;T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.6

L;L;L

PrimateAI

Uncertain

0.51

PROVEAN

Uncertain

-2.4

N;N;N

REVEL

Benign

0.20

Sift

Benign

0.039

D;D;D

Sift4G

Uncertain

0.015

D;D;D

Polyphen

0.72

P;.;P

Vest4

0.40

MutPred

0.45

Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);Loss of helix (P = 0.0444);

MVP

0.33

MPC

0.043

ClinPred

0.71

GERP RS

-3.5

Varity_R

0.36

gMVP

0.78

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

Computational scores

Splicing

Publications

Other links and lift over