2-174571942-TGAGGAG-TGAG

Variant names:

• chr2-174571942-TGAG-T
• rs556678311
• NM_001375834.1:c.860_862delCTC

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PM4_Supporting

The NM_001375834.1(WIPF1):​c.860_862delCTC​(p.Pro287del) variant causes a disruptive inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000434 in 1,589,356 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: WIPF1 NM_001375834.1 disruptive_inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 7.66
• Publications: 0 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• Wiskott-Aldrich syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236449 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001375834.1. Strenght limited to Supporting due to length of the change: 1aa.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001375834.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	NM_001375834.1	MANE Select	c.860_862delCTC	p.Pro287del	disruptive_inframe_deletion	Exon 5 of 8	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.860_862delCTC	p.Pro287del	disruptive_inframe_deletion	Exon 5 of 9	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.860_862delCTC	p.Pro287del	disruptive_inframe_deletion	Exon 5 of 8	NP_001070737.1	Q2YDC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000679041.1	MANE Select	c.860_862delCTC	p.Pro287del	disruptive_inframe_deletion	Exon 5 of 8	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000272746.9	TSL:1	c.860_862delCTC	p.Pro287del	disruptive_inframe_deletion	Exon 5 of 9	ENSP00000272746.5	O43516-3
	WIPF1	ENST00000359761.7	TSL:1	c.860_862delCTC	p.Pro287del	disruptive_inframe_deletion	Exon 5 of 8	ENSP00000352802.3	O43516-1

Frequencies

GnomAD3 genomes AF: 0.0000529 AC: 8 AN: 151224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000972

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000479

GnomAD2 exomes AF: 0.000135 AC: 30 AN: 221762 AF XY: 0.0000923

Gnomad AFR exome AF: 0.0000635

Gnomad AMR exome AF: 0.000164

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000622

Gnomad FIN exome AF: 0.0000528

Gnomad NFE exome AF: 0.0000495

Gnomad OTH exome AF: 0.000189

GnomAD4 exome AF: 0.0000424 AC: 61 AN: 1438016 Hom.: 0 AF XY: 0.0000336 AC XY: 24 AN XY: 713644

African (AFR) AF: 0.00 AC: 0 AN: 32794

American (AMR) AF: 0.0000965 AC: 4 AN: 41452

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23966

East Asian (EAS) AF: 0.000429 AC: 17 AN: 39610

South Asian (SAS) AF: 0.0000365 AC: 3 AN: 82234

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52278

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00000727 AC: 8 AN: 1100760

Other (OTH) AF: 0.000489 AC: 29 AN: 59326

GnomAD4 genome AF: 0.0000529 AC: 8 AN: 151340 Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4 AN XY: 73950

African (AFR) AF: 0.0000243 AC: 1 AN: 41144

American (AMR) AF: 0.0000656 AC: 1 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.000975 AC: 5 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67778

Other (OTH) AF: 0.000474 AC: 1 AN: 2108

Alfa AF: 0.000192 Hom.: 0

Bravo AF: 0.0000604

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	2	-	Wiskott-Aldrich syndrome 2 (2)
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7
Mutation Taster		=47/53	disease causing

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

Other links and lift over

dbSNP: rs556678311; hg19: chr2-175436670; COSMIC: COSV55821069; COSMIC: COSV55821069;