2-174566979-C-G

Variant names:

• chr2-174566979-C-G
• rs2163236
• ENST00000409891.5:c.*65G>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 6 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: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000409891.5. 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.1456+91G>C		intron	N/A	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.1456+91G>C		intron	N/A	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.1456+91G>C		intron	N/A	NP_001070737.1	Q2YDC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000409891.5	TSL:1	c.*65G>C		3_prime_UTR	Exon 7 of 7	ENSP00000386431.1	O43516-2
	WIPF1	ENST00000679041.1	MANE Select	c.1456+91G>C		intron	N/A	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000272746.9	TSL:1	c.1456+91G>C		intron	N/A	ENSP00000272746.5	O43516-3

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

African (AFR) AF: 0.333 AC: 8769 AN: 26296

American (AMR) AF: 0.622 AC: 21849 AN: 35140

Ashkenazi Jewish (ASJ) AF: 0.663 AC: 14750 AN: 22246

East Asian (EAS) AF: 0.857 AC: 31627 AN: 36900

South Asian (SAS) AF: 0.506 AC: 37176 AN: 73508

European-Finnish (FIN) AF: 0.586 AC: 29518 AN: 50338

Middle Eastern (MID) AF: 0.539 AC: 2657 AN: 4934

European-Non Finnish (NFE) AF: 0.502 AC: 417674 AN: 831204

Other (OTH) AF: 0.530 AC: 26026 AN: 49100

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

African (AFR) AF: 0.336 AC: 13935 AN: 41460

American (AMR) AF: 0.546 AC: 8331 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.669 AC: 2320 AN: 3468

East Asian (EAS) AF: 0.853 AC: 4421 AN: 5184

South Asian (SAS) AF: 0.507 AC: 2438 AN: 4812

European-Finnish (FIN) AF: 0.599 AC: 6332 AN: 10566

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.511 AC: 34739 AN: 67958

Other (OTH) AF: 0.522 AC: 1098 AN: 2104

Alfa AF: 0.486 Hom.: 2297

Bravo AF: 0.481

Asia WGS AF: 0.578 AC: 2011 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.7
DANN	Benign	0.45
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2163236; hg19: chr2-175431707;