2-174585532-C-G

Variant names:

• chr2-174585532-C-G
• rs111761533
• NM_001375834.1:c.42G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001375834.1(WIPF1):​c.42G>C​(p.Thr14Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. T14T) has been classified as Benign.

• Frequency:
  • Genomes: 𝑓 0.000015 (0 hom., cov: 28)
  • Exomes 𝑓: 0.0000094 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WIPF1 NM_001375834.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.16
• Publications: 1 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen
• Wiskott-Aldrich syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000236449 (HGNC:):

ENSG00000237798 (HGNC:40613):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WIPF1	NM_001375834.1	c.42G>C	p.Thr14Thr	synonymous_variant	Exon 2 of 8	ENST00000679041.1	NP_001362763.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WIPF1	ENST00000679041.1	c.42G>C	p.Thr14Thr	synonymous_variant	Exon 2 of 8		NM_001375834.1	ENSP00000503603.1

Frequencies

GnomAD3 genomes AF: 0.0000153 AC: 2 AN: 130418 Hom.: 0 Cov.: 28

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000830

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000268

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000944 AC: 9 AN: 953326 Hom.: 0 Cov.: 39 AF XY: 0.00000829 AC XY: 4 AN XY: 482256

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0000458 AC: 1 AN: 21848

American (AMR) AF: 0.00 AC: 0 AN: 35590

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15864

East Asian (EAS) AF: 0.00 AC: 0 AN: 16742

South Asian (SAS) AF: 0.00 AC: 0 AN: 77532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 32986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3978

European-Non Finnish (NFE) AF: 0.0000112 AC: 8 AN: 712752

Other (OTH) AF: 0.00 AC: 0 AN: 36034

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000153 AC: 2 AN: 130474 Hom.: 0 Cov.: 28 AF XY: 0.0000161 AC XY: 1 AN XY: 62136

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 35212

American (AMR) AF: 0.0000829 AC: 1 AN: 12066

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3268

East Asian (EAS) AF: 0.000268 AC: 1 AN: 3734

South Asian (SAS) AF: 0.00 AC: 0 AN: 3582

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6760

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 264

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 62936

Other (OTH) AF: 0.00 AC: 0 AN: 1806

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0000000000983081), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	1.3
DANN	Benign	0.68
PhyloP100		-1.2
PromoterAI		-0.012	Neutral
Mutation Taster		=100/0	polymorphism

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: rs111761533; hg19: chr2-175450260;