20-45479989-GGC-TCA

Variant names:

• chr20-45479989-GGC-TCA
• NM_006103.4:c.271_273delGGCinsTCA
• WFDC2 p.Gly91Ser

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_006103.4(WFDC2):​c.271_273delGGCinsTCA​(p.Gly91Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WFDC2 NM_006103.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006103.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC2	NM_006103.4	MANE Select	c.271_273delGGCinsTCA	p.Gly91Ser	missense	N/A	NP_006094.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WFDC2	ENST00000372676.8	TSL:1 MANE Select	c.271_273delGGCinsTCA	p.Gly91Ser	missense	N/A	ENSP00000361761.3	Q14508-1
	WFDC2	ENST00000339946.7	TSL:1	c.127_129delGGCinsTCA	p.Gly43Ser	missense	N/A	ENSP00000340215.3	Q14508-3
	WFDC2	ENST00000342873.7	TSL:1	c.118_120delGGCinsTCA	p.Gly40Ser	missense	N/A	ENSP00000342890.3	Q14508-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr20-44108629;