2-174630583-C-T

Position:

• chr2-174630583-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001375835.1(WIPF1):​c.-38-44972G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,994 control chromosomes in the GnomAD database, including 8,008 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.30 (8008 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WIPF1 NM_001375835.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20

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]

ENSG00000236449 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.65 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF1	XM_047445750.1	c.-20022G>A		5_prime_UTR_premature_start_codon_gain_variant	1/13		XP_047301706.1
WIPF1	XM_047445751.1	c.-583G>A		5_prime_UTR_premature_start_codon_gain_variant	1/10		XP_047301707.1
WIPF1	XM_047445752.1	c.-3881G>A		5_prime_UTR_premature_start_codon_gain_variant	1/10		XP_047301708.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000272746.9	c.-38-44972G>A		intron_variant		1		ENSP00000272746.5
WIPF1	ENST00000359761.7	c.-38-44972G>A		intron_variant		1		ENSP00000352802.3
WIPF1	ENST00000392547.6	c.-39+3935G>A		intron_variant		1		ENSP00000376330.2

Frequencies

GnomAD3 genomes AF: 0.296 AC: 45000 AN: 151876 Hom.: 8000 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.448

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.668

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.256

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.294

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.296 AC: 45034 AN: 151994 Hom.: 8008 Cov.: 32 AF XY: 0.305 AC XY: 22666 AN XY: 74272

Gnomad4 AFR AF: 0.140

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.669

Gnomad4 SAS AF: 0.376

Gnomad4 FIN AF: 0.367

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.293

Alfa AF: 0.297 Hom.: 9530

Bravo AF: 0.297

Asia WGS AF: 0.478 AC: 1663 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.50
DANN	Benign	0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1991600; hg19: chr2-175495311;