rs10227271

chr7-117299994-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.95).
• 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/exons	MANE	UniProt
WNT2	NM_003391.3	c.589-2118T>C		intron_variant		ENST00000265441.8
LOC124900596	XR_927899.3	n.186-868A>G		intron_variant, non_coding_transcript_variant
WNT2	NR_024047.2	n.594-2118T>C		intron_variant, non_coding_transcript_variant
LOC124900596	XR_927898.3	n.170-868A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WNT2	ENST00000265441.8	c.589-2118T>C		intron_variant		1	NM_003391.3	P1

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

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.301

Gnomad4 ASJ AF: 0.107

Gnomad4 EAS AF: 0.472

Gnomad4 SAS AF: 0.399

Gnomad4 FIN AF: 0.231

Gnomad4 NFE AF: 0.130

Gnomad4 OTH AF: 0.196

Alfa AF: 0.153 Hom.: 2373

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

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: rs10227271; hg19: chr7-116940048;