rs17132543

Variant names:

• chr7-117292480-A-G
• rs17132543
• NM_003391.3:c.853+5132T>C

Your query was ambiguous. Multiple possible variants found:

• chr7-117292480-A-G
• chr7-117292480-A-T

Variant summary

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

The NM_003391.3(WNT2):​c.853+5132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,220 control chromosomes in the GnomAD database, including 1,783 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 0.12 (1783 hom., cov: 32)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• 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]

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)

LOC124900596 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 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.853+5132T>C		intron	N/A	NP_003382.1	P09544
	WNT2	NR_024047.2		n.858+5132T>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	ENST00000265441.8	TSL:1 MANE Select	c.853+5132T>C		intron	N/A	ENSP00000265441.3	P09544
	CFTR	ENST00000673785.1		c.-660+5315A>G		intron	N/A	ENSP00000501235.1	A0A669KBE8
	WNT2	ENST00000950642.1		c.562+5132T>C		intron	N/A	ENSP00000620701.1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18134 AN: 152102 Hom.: 1771 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.119 AC: 18164 AN: 152220 Hom.: 1783 Cov.: 32 AF XY: 0.129 AC XY: 9615 AN XY: 74426

African (AFR) AF: 0.0615 AC: 2556 AN: 41540

American (AMR) AF: 0.245 AC: 3749 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0711 AC: 247 AN: 3472

East Asian (EAS) AF: 0.439 AC: 2266 AN: 5166

South Asian (SAS) AF: 0.363 AC: 1747 AN: 4810

European-Finnish (FIN) AF: 0.0978 AC: 1038 AN: 10610

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0924 AC: 6285 AN: 68020

Other (OTH) AF: 0.108 AC: 227 AN: 2106

Alfa AF: 0.122 Hom.: 646

Bravo AF: 0.126

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.47
PhyloP100		-0.13
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: rs17132543; hg19: chr7-116932534;