chr6-110100644-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PVS1_ModeratePM2PP5

The NM_003931.3(WASF1):​c.1558C>T​(p.Gln520Ter) variant causes a stop gained change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: not found (cov: 32)

Consequence

WASF1
NM_003931.3 stop_gained

Scores

5
1
1

Clinical Significance

Pathogenic no assertion criteria provided P:3

Conservation

PhyloP100: 9.54
Variant links:
Genes affected
WASF1 (HGNC:12732): (WASP family member 1) The protein encoded by this gene, a member of the Wiskott-Aldrich syndrome protein (WASP)-family, plays a critical role downstream of Rac, a Rho-family small GTPase, in regulating the actin cytoskeleton required for membrane ruffling. It has been shown to associate with an actin nucleation core Arp2/3 complex while enhancing actin polymerization in vitro. Wiskott-Aldrich syndrome is a disease of the immune system, likely due to defects in regulation of actin cytoskeleton. Multiple alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 5 ACMG points.

PVS1
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0726 CDS is truncated, and there are 2 pathogenic variants in the truncated region.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 6-110100644-G-A is Pathogenic according to our data. Variant chr6-110100644-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 561981.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr6-110100644-G-A is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
WASF1NM_003931.3 linkuse as main transcriptc.1558C>T p.Gln520Ter stop_gained 11/11 ENST00000392589.6
WASF1NM_001024934.2 linkuse as main transcriptc.1558C>T p.Gln520Ter stop_gained 10/10
WASF1NM_001024935.2 linkuse as main transcriptc.1558C>T p.Gln520Ter stop_gained 10/10
WASF1NM_001024936.2 linkuse as main transcriptc.1558C>T p.Gln520Ter stop_gained 9/9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
WASF1ENST00000392589.6 linkuse as main transcriptc.1558C>T p.Gln520Ter stop_gained 11/115 NM_003931.3 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
30
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:3
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Neurodevelopmental disorder with absent language and variable seizures Pathogenic:1
Pathogenic, no assertion criteria providedliterature onlyOMIMDec 20, 2019- -
Epileptic encephalopathy Pathogenic:1
Pathogenic, no assertion criteria providedresearchNIHR Bioresource Rare Diseases, University of Cambridge-- -
Intellectual disability Pathogenic:1
Pathogenic, no assertion criteria providedresearchNIHR Bioresource Rare Diseases, University of CambridgeJan 01, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
0.62
D
BayesDel_noAF
Pathogenic
0.66
CADD
Pathogenic
41
DANN
Uncertain
1.0
Eigen
Pathogenic
1.2
Eigen_PC
Pathogenic
1.1
FATHMM_MKL
Pathogenic
0.99
D
MutationTaster
Benign
1.0
D;D;D;D;D
Vest4
0.80
GERP RS
5.6

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: rs1562159088; hg19: chr6-110421847; API