chr17-40260578-G-T

Variant names:

• chr17-40260578-G-T
• NM_133264.5:c.107G>T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_133264.5(WIPF2):​c.107G>T​(p.Gly36Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 28)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: WIPF2 NM_133264.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133264.5. 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
	WIPF2	NM_133264.5	MANE Select	c.107G>T	p.Gly36Val	missense	Exon 3 of 8	NP_573571.1	Q8TF74-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF2	ENST00000323571.9	TSL:1 MANE Select	c.107G>T	p.Gly36Val	missense	Exon 3 of 8	ENSP00000320924.4	Q8TF74-1
	WIPF2	ENST00000585043.5	TSL:1	c.107G>T	p.Gly36Val	missense	Exon 3 of 8	ENSP00000462826.1	Q8TF74-1
	WIPF2	ENST00000494757.5	TSL:1	n.215G>T		non_coding_transcript_exon	Exon 2 of 7

Frequencies

GnomAD3 genomes Cov.: 28

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461862 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727232

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111990

Other (OTH) AF: 0.00 AC: 0 AN: 60394

GnomAD4 genome Cov.: 28

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.58
BayesDel_addAF	Uncertain	0.072	D
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.54	D
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.067	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.46	T
MutationAssessor	Pathogenic	3.7	H
PhyloP100		4.9
PrimateAI	Uncertain	0.65	T
PROVEAN	Pathogenic	-6.7	D
REVEL	Uncertain	0.37
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.72
MutPred		0.53		Gain of helix (P = 0.0496)
MVP		0.80
MPC		0.69
ClinPred		1.0	D
GERP RS		2.2
Varity_R		0.65
gMVP		0.32
Mutation Taster		=63/37	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

hg19: chr17-38416830;