Variant 2-174571942-T-TGAG details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM2PM4_SupportingPP3BP6_Moderate

The NM_001375834.1(WIPF1):c.862_863insCTC(p.Pro287dup) variant causes a inframe insertion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000692 in 1,589,418 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00025 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000050 ( 0 hom. )

Consequence

WIPF1
NM_001375834.1 inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.66

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 links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PM4

Nonframeshift variant in NON repetitive region in NM_001375834.1. Strenght limited to Supporting due to length of the change: 1aa.

PP3

No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

BP6

Variant 2-174571942-T-TGAG is Benign according to our data. Variant chr2-174571942-T-TGAG is described in ClinVar as [Likely_benign]. Clinvar id is 540147.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF1	NM_001375834.1 linkuse as main transcript	c.862_863insCTC	p.Pro287dup	inframe_insertion	5/8	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1 linkuse as main transcript	c.862_863insCTC	p.Pro287dup	inframe_insertion	5/8		NM_001375834.1	ENSP00000503603	P3	O43516-1
	ENST00000442996.1 linkuse as main transcript	n.217+24476_217+24478dup		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.000251

AC:

AN:

151224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000460

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00175

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000275

AC:

AN:

221762

Hom.:

AF XY:

0.000243

AC XY:

AN XY:

119198

show subpopulations

Gnomad AFR exome

AF:

0.000571

Gnomad AMR exome

AF:

0.0000327

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00277

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000198

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000501

AC:

AN:

1438078

Hom.:

Cov.:

AF XY:

0.0000518

AC XY:

AN XY:

713678

show subpopulations

Gnomad4 AFR exome

AF:

0.000274

Gnomad4 AMR exome

AF:

0.0000482

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00104

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000506

GnomAD4 genome

AF:

0.000251

AC:

AN:

151340

Hom.:

Cov.:

AF XY:

0.000270

AC XY:

AN XY:

73950

show subpopulations

Gnomad4 AFR

AF:

0.000462

Gnomad4 AMR

AF:

0.000459

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00175

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Wiskott-Aldrich syndrome 2

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 10, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over