rs39312

Variant names:

• chr7-117314731-A-C
• rs39312
• NM_003391.3:c.588+340T>G

Your query was ambiguous. Multiple possible variants found:

• chr7-117314731-A-C
• chr7-117314731-A-G
• chr7-117314731-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.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
• Publications: 14 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), Laboratory for Molecular Medicine, Myriad Women’s Health
• 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)

LOC105375467 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

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.588+340T>G		intron	N/A	NP_003382.1	P09544
	WNT2	NR_024047.2		n.593+340T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2	ENST00000265441.8	TSL:1 MANE Select	c.588+340T>G		intron	N/A	ENSP00000265441.3	P09544
	CFTR	ENST00000673785.1		c.-491+13701A>C		intron	N/A	ENSP00000501235.1	A0A669KBE8
	WNT2	ENST00000950642.1		c.297+340T>G		intron	N/A	ENSP00000620701.1

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

African (AFR) AF: 0.517 AC: 21428 AN: 41426

American (AMR) AF: 0.454 AC: 6931 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 858 AN: 3472

East Asian (EAS) AF: 0.426 AC: 2196 AN: 5152

South Asian (SAS) AF: 0.467 AC: 2255 AN: 4824

European-Finnish (FIN) AF: 0.418 AC: 4426 AN: 10576

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.371 AC: 25210 AN: 67962

Other (OTH) AF: 0.411 AC: 867 AN: 2112

Alfa AF: 0.379 Hom.: 14867

Bravo AF: 0.427

Asia WGS AF: 0.481 AC: 1677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.41
PhyloP100		-0.050
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: rs39312; hg19: chr7-116954785;