17-40264744-C-A

Position:

• chr17-40264744-C-A

Variant summary

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

The NM_133264.5(WIPF2):​c.568C>A​(p.Pro190Thr) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 29)
• Consequence: WIPF2 NM_133264.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.97

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=0.3490928).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF2	NM_133264.5	c.568C>A	p.Pro190Thr	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.568C>A	p.Pro190Thr	missense_variant	5/8	1	NM_133264.5	ENSP00000320924.4

Frequencies

GnomAD3 genomes Cov.: 29

GnomAD4 exome Cov.: 36

GnomAD4 genome Cov.: 29

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

Aug 12, 2024

The c.568C>A (p.P190T) alteration is located in exon 5 (coding exon 4) of the WIPF2 gene. This alteration results from a C to A substitution at nucleotide position 568, causing the proline (P) at amino acid position 190 to be replaced by a threonine (T). 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	0.069
BayesDel_addAF	Benign	-0.099	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.43	T;T;T
Eigen	Benign	-0.13
Eigen_PC	Benign	-0.14
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.76	.;.;T
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.35	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.7	M;M;M
PrimateAI	Uncertain	0.53	T
PROVEAN	Uncertain	-3.0	D;.;.
REVEL	Benign	0.12
Sift	Uncertain	0.0030	D;.;.
Sift4G	Uncertain	0.028	D;D;D
Polyphen		0.91	P;P;P
Vest4		0.45
MutPred		0.24		Loss of catalytic residue at P189 (P = 0.0283);Loss of catalytic residue at P189 (P = 0.0283);Loss of catalytic residue at P189 (P = 0.0283);
MVP		0.47
MPC		0.48
ClinPred		0.95	D
GERP RS		1.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.20
gMVP		0.24

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: chr17-38420996;