Genetic Variant NM_006990.5:c.1259T>C (chr1-27409772-A-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_006990.5(WASF2):c.1259T>C(p.Leu420Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000137 in 1,391,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

WASF2
NM_006990.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0670

Publications

0 publications found

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 was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02987799).

BS2

High AC in GnomAdExome4 at 19 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006990.5. 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
	WASF2	NM_006990.5	MANE Select	c.1259T>C	p.Leu420Pro	missense	Exon 8 of 9	NP_008921.1	Q9Y6W5-1
	WASF2	NM_001201404.3		c.825-1426T>C		intron	N/A	NP_001188333.1	Q9Y6W5-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WASF2	ENST00000618852.5	TSL:1 MANE Select	c.1259T>C	p.Leu420Pro	missense	Exon 8 of 9	ENSP00000483313.1	Q9Y6W5-1
WASF2	ENST00000874253.1		c.1259T>C	p.Leu420Pro	missense	Exon 9 of 10	ENSP00000544312.1
WASF2	ENST00000874254.1		c.1259T>C	p.Leu420Pro	missense	Exon 9 of 10	ENSP00000544313.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000152

AC:

AN:

196790

AF XY:

0.00000956

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000400

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000216

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1391248

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

684896

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31242

American (AMR)

AF:

0.0000293

AC:

AN:

34096

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21312

East Asian (EAS)

AF:

0.00

AC:

AN:

38948

South Asian (SAS)

AF:

0.0000135

AC:

AN:

74184

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51094

Middle Eastern (MID)

AF:

0.000370

AC:

AN:

5410

European-Non Finnish (NFE)

AF:

0.0000130

AC:

AN:

1077648

Other (OTH)

AF:

0.0000174

AC:

AN:

57314

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000248

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.051

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.2

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.064

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.47

M_CAP

Benign

0.0034

MetaRNN

Benign

0.030

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

PhyloP100

-0.067

PrimateAI

Benign

0.37

Sift4G

Benign

0.34

Polyphen

0.0

Vest4

0.044

MVP

0.043

ClinPred

0.018

GERP RS

-2.0

Varity_R

0.034

gMVP

0.16

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over