chr16-69798718-C-T

Position:

• chr16-69798718-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001270454.2(WWP2):​c.107C>T​(p.Pro36Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WWP2 NM_001270454.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.15

Genes affected

WWP2 (HGNC:16804): (WW domain containing E3 ubiquitin protein ligase 2) This gene encodes a member of the Nedd4 family of E3 ligases, which play an important role in protein ubiquitination. The encoded protein contains four WW domains and may play a role in multiple processes including chondrogenesis and the regulation of oncogenic signaling pathways via interactions with Smad proteins and the tumor suppressor PTEN. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, and a pseudogene of this gene is located on the long arm of chromosome 10. [provided by RefSeq, Jul 2012]

WWP2 (HGNC:):

ACMG classification

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=0.24472946).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWP2	NM_001270454.2	c.107C>T	p.Pro36Leu	missense_variant	3/24	ENST00000359154.7	NP_001257383.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWP2	ENST00000359154.7	c.107C>T	p.Pro36Leu	missense_variant	3/24	1	NM_001270454.2	ENSP00000352069.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.107C>T (p.P36L) alteration is located in exon 4 (coding exon 2) of the WWP2 gene. This alteration results from a C to T substitution at nucleotide position 107, causing the proline (P) at amino acid position 36 to be replaced by a leucine (L). 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	0.076
BayesDel_addAF	Benign	-0.015	T
BayesDel_noAF	Benign	-0.26
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;T;T;.
Eigen	Benign	-0.22
Eigen_PC	Benign	0.013
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L;.;.;L
PrimateAI	Benign	0.45	T
PROVEAN	Benign	1.4	N;N;D;N
REVEL	Benign	0.13
Sift	Benign	0.86	T;T;D;T
Sift4G	Benign	0.70	T;D;D;T
Polyphen		0.0060	B;.;.;.
Vest4		0.51
MutPred		0.54		Gain of catalytic residue at P36 (P = 0.0276);Gain of catalytic residue at P36 (P = 0.0276);Gain of catalytic residue at P36 (P = 0.0276);Gain of catalytic residue at P36 (P = 0.0276);
MVP		0.19
MPC		0.35
ClinPred		0.95	D
GERP RS		4.8
Varity_R		0.15
gMVP		0.33

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.

Other links and lift over

hg19: chr16-69832621;