2-174585532-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001375834.1(WIPF1):c.42G>A(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,085,630 control chromosomes in the GnomAD database, including 30 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0090 ( 20 hom., cov: 28)

Exomes 𝑓: 0.0012 ( 10 hom. )

Consequence

WIPF1
NM_001375834.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.16

Publications

1 publications found

Variant links:

Genes affected

WIPF1 (HGNC:12736): (WAS/WASL interacting protein family member 1) This gene encodes a protein that plays an important role in the organization of the actin cytoskeleton. The encoded protein binds to a region of Wiskott-Aldrich syndrome protein that is frequently mutated in Wiskott-Aldrich syndrome, an X-linked recessive disorder. Impairment of the interaction between these two proteins may contribute to the disease. Two transcript variants encoding the same protein have been identified for this gene. [provided by RefSeq, Jul 2008]

WIPF1 Gene-Disease associations (from GenCC):

Wiskott-Aldrich syndrome 2
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
Wiskott-Aldrich syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

WIPF1 links:

ENSG00000236449 (HGNC:):

ENSG00000236449 links:

ENSG00000237798 (HGNC:40613):

ENSG00000237798 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.6).

BP6

Variant 2-174585532-C-T is Benign according to our data. Variant chr2-174585532-C-T is described in ClinVar as Benign. ClinVar VariationId is 472922.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.16 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00905 (1181/130498) while in subpopulation AFR AF = 0.0321 (1131/35202). AF 95% confidence interval is 0.0306. There are 20 homozygotes in GnomAd4. There are 562 alleles in the male GnomAd4 subpopulation. Median coverage is 28. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 20 AR,AD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF1	NM_001375834.1 link	c.42G>A	p.Thr14Thr	synonymous_variant	Exon 2 of 8	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1 link	c.42G>A	p.Thr14Thr	synonymous_variant	Exon 2 of 8		NM_001375834.1	ENSP00000503603.1

Frequencies

GnomAD3 genomes

AF:

0.00905

AC:

1181

AN:

130440

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0322

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00232

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000557

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000794

Gnomad OTH

AF:

0.00837

GnomAD2 exomes

AF:

0.00215

AC:

525

AN:

244346

AF XY:

0.00151

show subpopulations

Gnomad AFR exome

AF:

0.0299

Gnomad AMR exome

AF:

0.00120

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000450

Gnomad OTH exome

AF:

0.00134

GnomAD4 exome

AF:

0.00119

AC:

1140

AN:

955132

Hom.:

Cov.:

AF XY:

0.00101

AC XY:

486

AN XY:

483122

show subpopulations

African (AFR)

AF:

0.0421

AC:

920

AN:

21874

American (AMR)

AF:

0.00188

AC:

AN:

35604

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15906

East Asian (EAS)

AF:

0.00

AC:

AN:

16776

South Asian (SAS)

AF:

0.000116

AC:

AN:

77594

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33006

Middle Eastern (MID)

AF:

0.00100

AC:

AN:

3988

European-Non Finnish (NFE)

AF:

0.0000518

AC:

AN:

714282

Other (OTH)

AF:

0.00285

AC:

103

AN:

36102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

137

183

229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

120

150

<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:

0.00905

AC:

1181

AN:

130498

Hom.:

Cov.:

AF XY:

0.00904

AC XY:

562

AN XY:

62148

show subpopulations

African (AFR)

AF:

0.0321

AC:

1131

AN:

35202

American (AMR)

AF:

0.00232

AC:

AN:

12074

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3268

East Asian (EAS)

AF:

0.00

AC:

AN:

3744

South Asian (SAS)

AF:

0.000557

AC:

AN:

3590

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6762

Middle Eastern (MID)

AF:

0.00

AC:

AN:

264

European-Non Finnish (NFE)

AF:

0.0000794

AC:

AN:

62940

Other (OTH)

AF:

0.00830

AC:

AN:

1808

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

106

160

213

266

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.00333

Hom.:

Bravo

AF:

0.00950

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Wiskott-Aldrich syndrome 2

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

WIPF1-related disorder

Benign:1

Jul 15, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.4

(source)

DANN

Benign

0.86

PhyloP100

-1.2

PromoterAI

-0.057

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

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

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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