7-117303081-C-T

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

LOC105375467 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2	NM_003391.3	c.589-5205G>A		intron_variant	Intron 3 of 4	ENST00000265441.8	NP_003382.1
WNT2	NR_024047.2	n.594-5205G>A		intron_variant	Intron 3 of 4
LOC105375467	XR_007060645.1	n.79+2051C>T		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT2	ENST00000265441.8	c.589-5205G>A		intron_variant	Intron 3 of 4	1	NM_003391.3	ENSP00000265441.3

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

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.405

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.562

Gnomad4 SAS AF: 0.351

Gnomad4 FIN AF: 0.452

Gnomad4 NFE AF: 0.396

Gnomad4 OTH AF: 0.432

Alfa AF: 0.408 Hom.: 28559

Bravo AF: 0.437

Asia WGS AF: 0.409 AC: 1421 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.24
DANN	Benign	0.27

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

Publications

LitVar

Other links and lift over

dbSNP: rs6947329; hg19: chr7-116943135;