7-117290908-A-G

Variant names:

• chr7-117290908-A-G
• rs3779547
• NM_003391.3:c.853+6704T>C

Variant summary

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

The ENST00000265441.8(WNT2):​c.853+6704T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 152,148 control chromosomes in the GnomAD database, including 19,483 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 0.50 (19483 hom., cov: 33)
• Consequence: WNT2 ENST00000265441.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 7 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.513 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+6704T>C		intron	N/A	NP_003382.1
	WNT2	NR_024047.2		n.858+6704T>C		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+6704T>C		intron	N/A	ENSP00000265441.3
	CFTR	ENST00000673785.1		c.-660+3743A>G		intron	N/A	ENSP00000501235.1
	CFTR	ENST00000436097.2	TSL:2	n.38+3743A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.502 AC: 76299 AN: 152030 Hom.: 19463 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.614

Gnomad AMR AF: 0.441

Gnomad ASJ AF: 0.537

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.634

Gnomad MID AF: 0.570

Gnomad NFE AF: 0.505

Gnomad OTH AF: 0.521

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

GnomAD4 genome AF: 0.502 AC: 76354 AN: 152148 Hom.: 19483 Cov.: 33 AF XY: 0.504 AC XY: 37463 AN XY: 74374

African (AFR) AF: 0.519 AC: 21541 AN: 41508

American (AMR) AF: 0.441 AC: 6739 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.537 AC: 1864 AN: 3470

East Asian (EAS) AF: 0.325 AC: 1685 AN: 5180

South Asian (SAS) AF: 0.339 AC: 1635 AN: 4818

European-Finnish (FIN) AF: 0.634 AC: 6705 AN: 10578

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.505 AC: 34356 AN: 67982

Other (OTH) AF: 0.520 AC: 1100 AN: 2114

Alfa AF: 0.500 Hom.: 4251

Bravo AF: 0.491

Asia WGS AF: 0.374 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.89
DANN	Benign	0.45
PhyloP100		-0.26
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: rs3779547; hg19: chr7-116930962;