chr7-117292480-A-G

Position:

• chr7-117292480-A-G

Variant summary

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

The ENST00000265441.8(WNT2):​c.853+5132T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 152,220 control chromosomes in the GnomAD database, including 1,783 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 0.12 (1783 hom., cov: 32)
• Consequence: WNT2 ENST00000265441.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.424 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT2	NM_003391.3	c.853+5132T>C		intron_variant		ENST00000265441.8	NP_003382.1
LOC124900596	XR_927899.3	n.39+5315A>G		intron_variant, non_coding_transcript_variant
WNT2	NR_024047.2	n.858+5132T>C		intron_variant, non_coding_transcript_variant
LOC124900596	XR_927898.3	n.82+1571A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT2	ENST00000265441.8	c.853+5132T>C		intron_variant		1	NM_003391.3	ENSP00000265441	P1

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18134 AN: 152102 Hom.: 1771 Cov.: 32

Gnomad AFR AF: 0.0615

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.244

Gnomad ASJ AF: 0.0711

Gnomad EAS AF: 0.439

Gnomad SAS AF: 0.362

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0924

Gnomad OTH AF: 0.107

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

GnomAD4 genome AF: 0.119 AC: 18164 AN: 152220 Hom.: 1783 Cov.: 32 AF XY: 0.129 AC XY: 9615 AN XY: 74426

Gnomad4 AFR AF: 0.0615

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.0711

Gnomad4 EAS AF: 0.439

Gnomad4 SAS AF: 0.363

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.0924

Gnomad4 OTH AF: 0.108

Alfa AF: 0.103 Hom.: 185

Bravo AF: 0.126

Asia WGS AF: 0.394 AC: 1369 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.14
DANN	Benign	0.47

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: rs17132543; hg19: chr7-116932534;