chr1-27409854-G-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_006990.5(WASF2):​c.1177C>A​(p.Pro393Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,550,290 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

WASF2
NM_006990.5 missense

Scores

1
6
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.20
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAdExome4 at 37 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WASF2NM_006990.5 linkuse as main transcriptc.1177C>A p.Pro393Thr missense_variant 8/9 ENST00000618852.5
WASF2NM_001201404.3 linkuse as main transcriptc.825-1508C>A intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WASF2ENST00000618852.5 linkuse as main transcriptc.1177C>A p.Pro393Thr missense_variant 8/91 NM_006990.5 P1Q9Y6W5-1
WASF2ENST00000536657.1 linkuse as main transcriptc.825-1508C>A intron_variant 2 Q9Y6W5-2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152076
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
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:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000246
AC:
5
AN:
202942
Hom.:
0
AF XY:
0.0000187
AC XY:
2
AN XY:
107006
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000536
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000265
AC:
37
AN:
1398214
Hom.:
0
Cov.:
32
AF XY:
0.0000306
AC XY:
21
AN XY:
686756
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000325
Gnomad4 OTH exome
AF:
0.0000347
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152076
Hom.:
0
Cov.:
31
AF XY:
0.0000269
AC XY:
2
AN XY:
74306
show subpopulations
Gnomad4 AFR
AF:
0.00
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:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000143
Hom.:
0
Bravo
AF:
0.0000340
ExAC
AF:
0.0000332
AC:
4

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMar 01, 2024The c.1177C>A (p.P393T) alteration is located in exon 8 (coding exon 7) of the WASF2 gene. This alteration results from a C to A substitution at nucleotide position 1177, causing the proline (P) at amino acid position 393 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
0.24
BayesDel_addAF
Uncertain
0.078
D
BayesDel_noAF
Benign
-0.13
CADD
Benign
23
DANN
Benign
0.95
DEOGEN2
Benign
0.41
T
Eigen
Uncertain
0.57
Eigen_PC
Uncertain
0.51
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.73
T
M_CAP
Benign
0.035
D
MetaRNN
Uncertain
0.56
D
MetaSVM
Benign
-0.67
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.73
T
Sift4G
Uncertain
0.030
D
Polyphen
1.0
D
Vest4
0.62
MVP
0.20
ClinPred
0.35
T
GERP RS
3.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.12
gMVP
0.37

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.

Other links and lift over

dbSNP: rs746315475; hg19: chr1-27736348; API