rs3779548

Variant names:

• chr7-117290841-T-C
• rs3779548
• NM_003391.3:c.853+6771A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265441.8(WNT2):​c.853+6771A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.474 in 152,030 control chromosomes in the GnomAD database, including 17,405 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 0.47 (17405 hom., cov: 32)
• Consequence: WNT2 ENST00000265441.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.722
• Publications: 6 publications found

Genes affected

WNT2 (HGNC:12780): (Wnt family member 2) This gene is a member of the WNT gene family. The WNT gene family consists of structurally related genes which encode secreted signaling proteins. These proteins have been implicated in oncogenesis and in several developmental processes, including regulation of cell fate and patterning during embryogenesis. Alternatively spliced transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

LOC124900596 (HGNC:):

CFTR (HGNC:1884): (CF transmembrane conductance regulator) This gene encodes a member of the ATP-binding cassette (ABC) transporter superfamily. The encoded protein functions as a chloride channel, making it unique among members of this protein family, and controls ion and water secretion and absorption in epithelial tissues. Channel activation is mediated by cycles of regulatory domain phosphorylation, ATP-binding by the nucleotide-binding domains, and ATP hydrolysis. Mutations in this gene cause cystic fibrosis, the most common lethal genetic disorder in populations of Northern European descent. The most frequently occurring mutation in cystic fibrosis, DeltaF508, results in impaired folding and trafficking of the encoded protein. Multiple pseudogenes have been identified in the human genome. [provided by RefSeq, Aug 2017]

CFTR Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Orphanet
• congenital bilateral absence of vas deferens

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• hereditary chronic pancreatitis

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265441.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	NM_003391.3	MANE Select	c.853+6771A>G		intron	N/A	NP_003382.1
	WNT2	NR_024047.2		n.858+6771A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	ENST00000265441.8	TSL:1 MANE Select	c.853+6771A>G		intron	N/A	ENSP00000265441.3
	CFTR	ENST00000673785.1		c.-660+3676T>C		intron	N/A	ENSP00000501235.1
	CFTR	ENST00000436097.2	TSL:2	n.38+3676T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.474 AC: 72026 AN: 151912 Hom.: 17399 Cov.: 32

Gnomad AFR AF: 0.468

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.421

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.321

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.484

Gnomad OTH AF: 0.491

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.474 AC: 72057 AN: 152030 Hom.: 17405 Cov.: 32 AF XY: 0.477 AC XY: 35430 AN XY: 74314

African (AFR) AF: 0.468 AC: 19394 AN: 41424

American (AMR) AF: 0.421 AC: 6426 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1750 AN: 3470

East Asian (EAS) AF: 0.327 AC: 1692 AN: 5176

South Asian (SAS) AF: 0.320 AC: 1542 AN: 4812

European-Finnish (FIN) AF: 0.622 AC: 6579 AN: 10576

Middle Eastern (MID) AF: 0.571 AC: 168 AN: 294

European-Non Finnish (NFE) AF: 0.484 AC: 32922 AN: 67974

Other (OTH) AF: 0.491 AC: 1039 AN: 2116

Alfa AF: 0.467 Hom.: 6608

Bravo AF: 0.460

Asia WGS AF: 0.362 AC: 1255 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.80
DANN	Benign	0.46
PhyloP100		-0.72
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: rs3779548; hg19: chr7-116930895; COSMIC: COSV55410708;