rs139822756

Variant names:

• chr17-40262528-C-G
• rs139822756
• NM_133264.5:c.200C>G

Your query was ambiguous. Multiple possible variants found:

• chr17-40262528-C-G
• chr17-40262528-C-T

Variant summary

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

The NM_133264.5(WIPF2):​c.200C>G​(p.Pro67Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000131 in 152,160 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.000013 (0 hom., cov: 31)
• Consequence: WIPF2 NM_133264.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.51

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

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=0.33319467).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF2	NM_133264.5	c.200C>G	p.Pro67Arg	missense_variant	Exon 4 of 8	ENST00000323571.9	NP_573571.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF2	ENST00000323571.9	c.200C>G	p.Pro67Arg	missense_variant	Exon 4 of 8	1	NM_133264.5	ENSP00000320924.4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152160 Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2 AN XY: 74332

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.22
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.35	T;T;T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.48
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.82	.;.;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.33	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.2	M;M;M;.
PrimateAI	Uncertain	0.49	T
PROVEAN	Pathogenic	-4.8	D;.;.;.
REVEL	Benign	0.078
Sift	Uncertain	0.0020	D;.;.;.
Sift4G	Benign	0.17	T;T;T;T
Polyphen		0.94	P;P;P;.
Vest4		0.46
MutPred		0.26		Gain of MoRF binding (P = 0.0248);Gain of MoRF binding (P = 0.0248);Gain of MoRF binding (P = 0.0248);Gain of MoRF binding (P = 0.0248);
MVP		0.75
MPC		0.33
ClinPred		0.97	D
GERP RS		5.2
Varity_R		0.38
gMVP		0.18

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

Publications

LitVar

Other links and lift over

dbSNP: rs139822756; hg19: chr17-38418780;