2-174566979-C-G

Position:

• chr2-174566979-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000409891.5(WIPF1):​c.*65G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 1,281,682 control chromosomes in the GnomAD database, including 177,513 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19193 hom., cov: 32)
  • Exomes 𝑓: 0.52 (158320 hom.)
• Consequence: WIPF1 ENST00000409891.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.330

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-174566979-C-G is Benign according to our data. Variant chr2-174566979-C-G is described in ClinVar as [Benign]. Clinvar id is 1263797.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.832 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WIPF1	NM_001375834.1	c.1456+91G>C		intron_variant		ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1	c.1456+91G>C		intron_variant			NM_001375834.1	ENSP00000503603	P3
	ENST00000442996.1	n.217+19502C>G		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.489 AC: 74245 AN: 151898 Hom.: 19195 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.542

Gnomad AMR AF: 0.546

Gnomad ASJ AF: 0.669

Gnomad EAS AF: 0.853

Gnomad SAS AF: 0.508

Gnomad FIN AF: 0.599

Gnomad MID AF: 0.516

Gnomad NFE AF: 0.511

Gnomad OTH AF: 0.525

GnomAD4 exome AF: 0.522 AC: 590046 AN: 1129666 Hom.: 158320 Cov.: 14 AF XY: 0.522 AC XY: 297832 AN XY: 570704

Gnomad4 AFR exome AF: 0.333

Gnomad4 AMR exome AF: 0.622

Gnomad4 ASJ exome AF: 0.663

Gnomad4 EAS exome AF: 0.857

Gnomad4 SAS exome AF: 0.506

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.502

Gnomad4 OTH exome AF: 0.530

GnomAD4 genome AF: 0.489 AC: 74261 AN: 152016 Hom.: 19193 Cov.: 32 AF XY: 0.493 AC XY: 36627 AN XY: 74296

Gnomad4 AFR AF: 0.336

Gnomad4 AMR AF: 0.546

Gnomad4 ASJ AF: 0.669

Gnomad4 EAS AF: 0.853

Gnomad4 SAS AF: 0.507

Gnomad4 FIN AF: 0.599

Gnomad4 NFE AF: 0.511

Gnomad4 OTH AF: 0.522

Alfa AF: 0.486 Hom.: 2297

Bravo AF: 0.481

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 82% of patients studied by a panel of primary immunodeficiencies. Number of patients: 72. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.45

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: rs2163236; hg19: chr2-175431707;