rs193922412

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_000377.3(WAS):c.1197_1205delACCGCCACC(p.Pro400_Pro402del) variant causes a disruptive inframe deletion change. The variant allele was found at a frequency of 0.000224 in 1,127,312 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 67 hemizygotes in GnomAD. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. P399P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., 1 hem., cov: 21)

Exomes 𝑓: 0.00023 ( 0 hom. 66 hem. )

Consequence

WAS
NM_000377.3 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.88

Publications

0 publications found

Variant links:

COSMIC-nc: COSV105927051

Genes affected

WAS (HGNC:12731): (WASP actin nucleation promoting factor) The Wiskott-Aldrich syndrome (WAS) family of proteins share similar domain structure, and are involved in transduction of signals from receptors on the cell surface to the actin cytoskeleton. The presence of a number of different motifs suggests that they are regulated by a number of different stimuli, and interact with multiple proteins. Recent studies have demonstrated that these proteins, directly or indirectly, associate with the small GTPase, Cdc42, known to regulate formation of actin filaments, and the cytoskeletal organizing complex, Arp2/3. Wiskott-Aldrich syndrome is a rare, inherited, X-linked, recessive disease characterized by immune dysregulation and microthrombocytopenia, and is caused by mutations in the WAS gene. The WAS gene product is a cytoplasmic protein, expressed exclusively in hematopoietic cells, which show signalling and cytoskeletal abnormalities in WAS patients. A transcript variant arising as a result of alternative promoter usage, and containing a different 5' UTR sequence, has been described, however, its full-length nature is not known. [provided by RefSeq, Jul 2008]

WAS Gene-Disease associations (from GenCC):

Wiskott-Aldrich syndrome
Inheritance: XL, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
X-linked severe congenital neutropenia
Inheritance: XL Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
thrombocytopenia 1
Inheritance: XL Classification: SUPPORTIVE Submitted by: Orphanet

WAS links:

ENSG00000232828 (HGNC:):

ENSG00000232828 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP6

Variant X-48688910-ACCACCACCG-A is Benign according to our data. Variant chrX-48688910-ACCACCACCG-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 36908.

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00015 (15/100128) while in subpopulation NFE AF = 0.000285 (14/49208). AF 95% confidence interval is 0.000171. There are 0 homozygotes in GnomAd4. There are 1 alleles in the male GnomAd4 subpopulation. Median coverage is 21. This position passed quality control check.

BS2

High AC in GnomAd4 at 15 XL,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WAS	NM_000377.3 link	c.1197_1205delACCGCCACC	p.Pro400_Pro402del	disruptive_inframe_deletion	Exon 10 of 12	ENST00000376701.5	NP_000368.1	P42768A0A024QYX8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WAS	ENST00000376701.5 link	c.1197_1205delACCGCCACC	p.Pro400_Pro402del	disruptive_inframe_deletion	Exon 10 of 12	1	NM_000377.3	ENSP00000365891.4		P42768

Frequencies

GnomAD3 genomes

AF:

0.000150

AC:

AN:

100112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000105

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:

0.000284

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000163

AC:

AN:

104064

AF XY:

0.000132

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000205

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000116

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000210

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

237

AN:

1027184

Hom.:

AF XY:

0.000203

AC XY:

AN XY:

325548

show subpopulations

African (AFR)

AF:

0.000122

AC:

AN:

24605

American (AMR)

AF:

0.000215

AC:

AN:

27878

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17190

East Asian (EAS)

AF:

0.0000384

AC:

AN:

26060

South Asian (SAS)

AF:

0.000251

AC:

AN:

47722

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3027

European-Non Finnish (NFE)

AF:

0.000260

AC:

209

AN:

804262

Other (OTH)

AF:

0.000141

AC:

AN:

42602

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.411

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.000150

AC:

AN:

100128

Hom.:

Cov.:

AF XY:

0.0000370

AC XY:

AN XY:

27012

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27037

American (AMR)

AF:

0.000105

AC:

AN:

9513

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2488

East Asian (EAS)

AF:

0.00

AC:

AN:

2895

South Asian (SAS)

AF:

0.00

AC:

AN:

1997

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4816

Middle Eastern (MID)

AF:

0.00

AC:

AN:

192

European-Non Finnish (NFE)

AF:

0.000285

AC:

AN:

49208

Other (OTH)

AF:

0.00

AC:

AN:

1364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.532

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000868

Hom.:

Bravo

AF:

0.000196

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 08, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Variant summary: WAS c.1197_1205delACCGCCACC (p.Pro402_Pro404del) results in an in-frame deletion that is predicted to remove 3 amino acids from the encoded protein. The variant allele was found at a frequency of 0.00016 in 104064 control chromosomes, predominantly at a frequency of 0.00033 within the South Asian subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1197_1205delACCGCCACC in individuals affected with Wiskott-Aldrich Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 36908). Based on the evidence outlined above, the variant was classified as uncertain significance. -

Wiskott-Aldrich syndrome;C1839163:Thrombocytopenia 1;C1845987:X-linked severe congenital neutropenia

Benign:1

Jan 11, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

6.9

Mutation Taster

=186/14

polymorphism

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over