7-117303081-C-T

Variant names:

• chr7-117303081-C-T
• rs6947329
• NM_003391.3:c.589-5205G>A

Variant summary

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

The NM_003391.3(WNT2):​c.589-5205G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.433 in 151,888 control chromosomes in the GnomAD database, including 14,454 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 0.43 (14454 hom., cov: 31)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.624
• Publications: 12 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]

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: Orphanet, Labcorp Genetics (formerly Invitae), Myriad Women’s Health, Laboratory for Molecular Medicine
• 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)

LOC105375467 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.545 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003391.3. 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
	WNT2	NM_003391.3	MANE Select	c.589-5205G>A		intron	N/A	NP_003382.1	P09544
	WNT2	NR_024047.2		n.594-5205G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	ENST00000265441.8	TSL:1 MANE Select	c.589-5205G>A		intron	N/A	ENSP00000265441.3	P09544
	CFTR	ENST00000673785.1		c.-491+2051C>T		intron	N/A	ENSP00000501235.1	A0A669KBE8
	WNT2	ENST00000950642.1		c.298-5205G>A		intron	N/A	ENSP00000620701.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65755 AN: 151770 Hom.: 14444 Cov.: 31

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.564

Gnomad AMR AF: 0.405

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.562

Gnomad SAS AF: 0.351

Gnomad FIN AF: 0.452

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.396

Gnomad OTH AF: 0.436

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

GnomAD4 genome AF: 0.433 AC: 65784 AN: 151888 Hom.: 14454 Cov.: 31 AF XY: 0.435 AC XY: 32315 AN XY: 74214

African (AFR) AF: 0.486 AC: 20145 AN: 41426

American (AMR) AF: 0.405 AC: 6178 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1672 AN: 3468

East Asian (EAS) AF: 0.562 AC: 2891 AN: 5142

South Asian (SAS) AF: 0.351 AC: 1687 AN: 4806

European-Finnish (FIN) AF: 0.452 AC: 4772 AN: 10546

Middle Eastern (MID) AF: 0.459 AC: 135 AN: 294

European-Non Finnish (NFE) AF: 0.396 AC: 26883 AN: 67932

Other (OTH) AF: 0.432 AC: 909 AN: 2102

Alfa AF: 0.411 Hom.: 43484

Bravo AF: 0.437

Asia WGS AF: 0.409 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.24
DANN	Benign	0.27
PhyloP100		-0.62
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: rs6947329; hg19: chr7-116943135;