2-174571944-AG-GA

Variant names:

• chr2-174571944-AG-GA
• NM_001375834.1:c.860_861delCTinsTC
• WIPF1 p.Pro287Leu

Variant summary

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

The NM_001375834.1(WIPF1):​c.860_861delCTinsTC​(p.Pro287Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P287S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WIPF1 NM_001375834.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.84
• 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 0 ACMG points.

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_861delCTinsTC	p.Pro287Leu	missense	N/A	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.860_861delCTinsTC	p.Pro287Leu	missense	N/A	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.860_861delCTinsTC	p.Pro287Leu	missense	N/A	NP_001070737.1	Q2YDC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000679041.1	MANE Select	c.860_861delCTinsTC	p.Pro287Leu	missense	N/A	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000272746.9	TSL:1	c.860_861delCTinsTC	p.Pro287Leu	missense	N/A	ENSP00000272746.5	O43516-3
	WIPF1	ENST00000359761.7	TSL:1	c.860_861delCTinsTC	p.Pro287Leu	missense	N/A	ENSP00000352802.3	O43516-1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		5.8

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-175436672;