17-40264574-G-C

Position:

• chr17-40264574-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_133264.5(WIPF2):​c.398G>C​(p.Arg133Pro) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: WIPF2 NM_133264.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.74

Genes affected

WIPF2 (HGNC:30923): (WAS/WASL interacting protein family member 2) This gene encodes a WASP interacting protein (WIP)-related protein. It has been shown that this protein has a role in the WASP-mediated organization of the actin cytoskeleton and that this protein is a potential link between the activated platelet-derived growth factor receptor and the actin polymerization machinery. [provided by RefSeq, Jul 2008]

WIPF2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.41668826).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF2	NM_133264.5	c.398G>C	p.Arg133Pro	missense_variant	5/8	ENST00000323571.9	NP_573571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF2	ENST00000323571.9	c.398G>C	p.Arg133Pro	missense_variant	5/8	1	NM_133264.5	ENSP00000320924.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

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

Feb 28, 2023

The c.398G>C (p.R133P) alteration is located in exon 5 (coding exon 4) of the WIPF2 gene. This alteration results from a G to C substitution at nucleotide position 398, causing the arginine (R) at amino acid position 133 to be replaced by a proline (P). 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	0.24
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.14	T;T;T
Eigen	Benign	0.13
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	.;.;T
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	0.69	N;.;.
REVEL	Benign	0.11
Sift	Uncertain	0.0030	D;.;.
Sift4G	Benign	0.34	T;T;T
Polyphen		0.0020	B;B;B
Vest4		0.65
MutPred		0.21		Loss of methylation at R133 (P = 0.0258);Loss of methylation at R133 (P = 0.0258);Loss of methylation at R133 (P = 0.0258);
MVP		0.51
MPC		0.71
ClinPred		0.94	D
GERP RS		5.2
Varity_R		0.33
gMVP		0.23

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: chr17-38420826;