2-174559701-G-A

Variant names:

• chr2-174559701-G-A
• rs7739
• NM_001375834.1:c.*2846C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001375834.1(WIPF1):​c.*2846C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.914 in 152,514 control chromosomes in the GnomAD database, including 63,914 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 0.91 (63754 hom., cov: 30)
  • Exomes 𝑓: 0.94 (160 hom.)
• Consequence: WIPF1 NM_001375834.1 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.55
• Publications: 5 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.34).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.937 is higher than 0.05.

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.*2846C>T		3_prime_UTR	Exon 8 of 8	NP_001362763.1	A0A140VJZ9
	WIPF1	NM_001375835.1		c.*2400C>T		3_prime_UTR	Exon 9 of 9	NP_001362764.1	O43516-3
	WIPF1	NM_001077269.1		c.*2846C>T		3_prime_UTR	Exon 8 of 8	NP_001070737.1	Q2YDC4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WIPF1	ENST00000679041.1	MANE Select	c.*2846C>T		3_prime_UTR	Exon 8 of 8	ENSP00000503603.1	O43516-1
	WIPF1	ENST00000392547.6	TSL:1	c.*2846C>T		3_prime_UTR	Exon 8 of 8	ENSP00000376330.2	O43516-1
	ENSG00000236449	ENST00000442996.1	TSL:1	n.217+12224G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.914 AC: 138999 AN: 152032 Hom.: 63716 Cov.: 30

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.968

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.954

Gnomad SAS AF: 0.826

Gnomad FIN AF: 0.961

Gnomad MID AF: 0.818

Gnomad NFE AF: 0.943

Gnomad OTH AF: 0.904

GnomAD4 exome AF: 0.937 AC: 341 AN: 364 Hom.: 160 Cov.: 0 AF XY: 0.932 AC XY: 207 AN XY: 222

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.936 AC: 337 AN: 360

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 1.00 AC: 4 AN: 4

GnomAD4 genome AF: 0.914 AC: 139089 AN: 152150 Hom.: 63754 Cov.: 30 AF XY: 0.914 AC XY: 67953 AN XY: 74374

African (AFR) AF: 0.853 AC: 35372 AN: 41486

American (AMR) AF: 0.930 AC: 14223 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3255 AN: 3472

East Asian (EAS) AF: 0.954 AC: 4943 AN: 5180

South Asian (SAS) AF: 0.826 AC: 3973 AN: 4808

European-Finnish (FIN) AF: 0.961 AC: 10186 AN: 10600

Middle Eastern (MID) AF: 0.818 AC: 239 AN: 292

European-Non Finnish (NFE) AF: 0.943 AC: 64114 AN: 68002

Other (OTH) AF: 0.901 AC: 1901 AN: 2110

Alfa AF: 0.933 Hom.: 66194

Bravo AF: 0.912

Asia WGS AF: 0.828 AC: 2878 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.34
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		1.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs7739; hg19: chr2-175424429;