rs3779547

chr7-117290908-A-Gchr7-117290908-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.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 NM_003391.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WNT2	NM_003391.3	c.853+6704T>C		intron_variant		ENST00000265441.8
LOC124900596	XR_927899.3	n.39+3743A>G		intron_variant, non_coding_transcript_variant
LOC124900596	XR_927898.3	n.81A>G		splice_region_variant, non_coding_transcript_exon_variant	1/3
WNT2	NR_024047.2	n.858+6704T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.853+6704T>C		intron_variant		1	NM_003391.3	P1

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

Gnomad4 AFR AF: 0.519

Gnomad4 AMR AF: 0.441

Gnomad4 ASJ AF: 0.537

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.634

Gnomad4 NFE AF: 0.505

Gnomad4 OTH AF: 0.520

Alfa AF: 0.500 Hom.: 4147

Bravo AF: 0.491

Asia WGS AF: 0.374 AC: 1298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.89
Dann	Benign	0.45

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: rs3779547; hg19: chr7-116930962;