chr2-174571942-TGAG-T

Position:

• chr2-174571942-TGAG-T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PM4_Supporting

The NM_001375834.1(WIPF1):​c.860_862del​(p.Pro287del) variant causes a 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 inframe_deletion
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• Conservation: PhyloP100: 7.66

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]

(HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 3 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF1	NM_001375834.1	c.860_862del	p.Pro287del	inframe_deletion	5/8	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1	c.860_862del	p.Pro287del	inframe_deletion	5/8		NM_001375834.1	ENSP00000503603	P3
	ENST00000442996.1	n.217+24476_217+24478del		intron_variant, non_coding_transcript_variant		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

GnomAD3 exomes AF: 0.000135 AC: 30 AN: 221762 Hom.: 0 AF XY: 0.0000923 AC XY: 11 AN XY: 119198

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 SAS exome AF: 0.000237

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000965

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000429

Gnomad4 SAS exome AF: 0.0000365

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000727

Gnomad4 OTH exome AF: 0.000489

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

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.0000656

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000975

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000474

Bravo AF: 0.0000604

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Wiskott-Aldrich syndrome 2 Uncertain:2

Uncertain significance, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Oct 04, 2022	This variant, c.860_862del, results in the deletion of 1 amino acid(s) of the WIPF1 protein (p.Pro287del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with WIPF1-related conditions. ClinVar contains an entry for this variant (Variation ID: 658041). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Uncertain significance, criteria provided, single submitter	clinical testing	Baylor Genetics	Nov 03, 2018	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Mayo Clinic Laboratories, Mayo Clinic

Mar 28, 2024

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs556678311; hg19: chr2-175436670;