rs10227271

Variant names:

• chr7-117299994-A-G
• rs10227271
• NM_003391.3:c.589-2118T>C

Variant summary

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

The NM_003391.3(WNT2):​c.589-2118T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,986 control chromosomes in the GnomAD database, including 5,076 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 0.23 (5076 hom., cov: 32)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.889
• 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]

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)

LOC124900596 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.456 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT2	NM_003391.3	c.589-2118T>C		intron_variant	Intron 3 of 4	ENST00000265441.8	NP_003382.1
WNT2	NR_024047.2	n.594-2118T>C		intron_variant	Intron 3 of 4
LOC124900596	XR_927898.3	n.170-868A>G		intron_variant	Intron 2 of 2
LOC124900596	XR_927899.3	n.186-868A>G		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT2	ENST00000265441.8	c.589-2118T>C		intron_variant	Intron 3 of 4	1	NM_003391.3	ENSP00000265441.3

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35301 AN: 151868 Hom.: 5036 Cov.: 32

Gnomad AFR AF: 0.344

Gnomad AMI AF: 0.0526

Gnomad AMR AF: 0.300

Gnomad ASJ AF: 0.107

Gnomad EAS AF: 0.472

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.233 AC: 35404 AN: 151986 Hom.: 5076 Cov.: 32 AF XY: 0.245 AC XY: 18181 AN XY: 74276

African (AFR) AF: 0.345 AC: 14296 AN: 41452

American (AMR) AF: 0.301 AC: 4590 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.107 AC: 372 AN: 3470

East Asian (EAS) AF: 0.472 AC: 2432 AN: 5152

South Asian (SAS) AF: 0.399 AC: 1919 AN: 4804

European-Finnish (FIN) AF: 0.231 AC: 2435 AN: 10552

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8864 AN: 67994

Other (OTH) AF: 0.196 AC: 412 AN: 2102

Alfa AF: 0.170 Hom.: 4261

Bravo AF: 0.241

Asia WGS AF: 0.472 AC: 1637 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	6.1
DANN	Benign	0.61
PhyloP100		0.89
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: rs10227271; hg19: chr7-116940048;