rs39312

Positions:

• chr7-117314731-A-C
• chr7-117314731-A-G
• chr7-117314731-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003391.3(WNT2):​c.588+340T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.424 in 152,004 control chromosomes in the GnomAD database, including 14,045 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 0.42 (14045 hom., cov: 32)
• Consequence: WNT2 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0500

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]

LOC105375467 (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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.511 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3	c.588+340T>G		intron_variant		ENST00000265441.8
LOC105375467	XR_007060645.1	n.80-7327A>C		intron_variant, non_coding_transcript_variant
WNT2	NR_024047.2	n.593+340T>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.588+340T>G		intron_variant		1	NM_003391.3	P1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64424 AN: 151884 Hom.: 14009 Cov.: 32

Gnomad AFR AF: 0.516

Gnomad AMI AF: 0.266

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.426

Gnomad SAS AF: 0.468

Gnomad FIN AF: 0.418

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.371

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.424 AC: 64518 AN: 152004 Hom.: 14045 Cov.: 32 AF XY: 0.427 AC XY: 31764 AN XY: 74318

Gnomad4 AFR AF: 0.517

Gnomad4 AMR AF: 0.454

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.426

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.418

Gnomad4 NFE AF: 0.371

Gnomad4 OTH AF: 0.411

Alfa AF: 0.369 Hom.: 10781

Bravo AF: 0.427

Asia WGS AF: 0.481 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.41

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: rs39312; hg19: chr7-116954785;