2-174566979-C-G

Variant names:

• chr2-174566979-C-G
• rs2163236
• ENST00000409891:c.*65G>C

Variant summary

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

The ENST00000409891(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 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]

ENSG00000236449 (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 rank	MANE	Protein	UniProt
WIPF1	NM_001375834.1	c.1456+91G>C		intron_variant	Intron 7 of 7	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1	c.1456+91G>C		intron_variant	Intron 7 of 7		NM_001375834.1	ENSP00000503603.1

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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;