Variant 1-27412656-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_006990.5(WASF2):c.740C>T(p.Pro247Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00137 in 1,614,176 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 8 hom. )

Consequence

WASF2
NM_006990.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.77

Variant links:

Genes affected

WASF2 (HGNC:12733): (WASP family member 2) This gene encodes a member of the Wiskott-Aldrich syndrome protein family. The gene product is a protein that forms a multiprotein complex that links receptor kinases and actin. Binding to actin occurs through a C-terminal verprolin homology domain in all family members. The multiprotein complex serves to tranduce signals that involve changes in cell shape, motility or function. The published map location (PMID:10381382) has been changed based on recent genomic sequence comparisons, which indicate that the expressed gene is located on chromosome 1, and a pseudogene may be located on chromosome X. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2011]

WASF2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0081346035).

BP6

Variant 1-27412656-G-A is Benign according to our data. Variant chr1-27412656-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 730779.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 163 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WASF2	NM_006990.5 link	c.740C>T	p.Pro247Leu	missense_variant	7/9	ENST00000618852.5	NP_008921.1	Q9Y6W5-1
WASF2	NM_001201404.3 link	c.740C>T	p.Pro247Leu	missense_variant	7/8		NP_001188333.1	Q9Y6W5-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WASF2	ENST00000618852.5 link	c.740C>T	p.Pro247Leu	missense_variant	7/9	1	NM_006990.5	ENSP00000483313.1		Q9Y6W5-1
WASF2	ENST00000536657.1 link	c.740C>T	p.Pro247Leu	missense_variant	7/8	2		ENSP00000439883.1		Q9Y6W5-2

Frequencies

GnomAD3 genomes

AF:

0.00108

AC:

164

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000393

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.000753

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00140

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00186

AC:

469

AN:

251496

Hom.:

AF XY:

0.00210

AC XY:

285

AN XY:

135922

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000318

Gnomad ASJ exome

AF:

0.00585

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00366

Gnomad FIN exome

AF:

0.000416

Gnomad NFE exome

AF:

0.00233

Gnomad OTH exome

AF:

0.00195

GnomAD4 exome

AF:

0.00140

AC:

2045

AN:

1461888

Hom.:

Cov.:

AF XY:

0.00149

AC XY:

1085

AN XY:

727242

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000313

Gnomad4 ASJ exome

AF:

0.00555

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00333

Gnomad4 FIN exome

AF:

0.000580

Gnomad4 NFE exome

AF:

0.00128

Gnomad4 OTH exome

AF:

0.00182

GnomAD4 genome

AF:

0.00107

AC:

163

AN:

152288

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000168

Gnomad4 AMR

AF:

0.000392

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00332

Gnomad4 FIN

AF:

0.000753

Gnomad4 NFE

AF:

0.00140

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00104

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.000778

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00267

AC:

ExAC

AF:

0.00239

AC:

290

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00207

EpiControl

AF:

0.00243

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Apr 02, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.40

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.041

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.85

T;D

M_CAP

Benign

0.0048

MetaRNN

Benign

0.0081

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Benign

0.47

PROVEAN

Uncertain

-2.9

.;D

REVEL

Benign

0.046

Sift

Benign

0.20

.;T

Sift4G

Benign

0.11

T;T

Polyphen

0.0060

B;.

Vest4

0.35

MVP

0.068

ClinPred

0.017

GERP RS

3.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.038

gMVP

0.79

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over