1-112509564-G-C

Variant names:

• chr1-112509564-G-C
• rs3790606
• NM_024494.3:c.182+120G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024494.3(WNT2B):​c.182+120G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.312 in 1,139,278 control chromosomes in the GnomAD database, including 57,456 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 0.27 (6316 hom., cov: 33)
  • Exomes 𝑓: 0.32 (51140 hom.)
• Consequence: WNT2B NM_024494.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.86
• Publications: 10 publications found

Genes affected

WNT2B (HGNC:12781): (Wnt family member 2B) This gene encodes a member of the wingless-type MMTV integration site (WNT) family of highly conserved, secreted signaling factors. WNT family members function in a variety of developmental processes including regulation of cell growth and differentiation and are characterized by a WNT-core domain. This gene may play a role in human development as well as carcinogenesis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]

WNT2B Gene-Disease associations (from GenCC):

• diarrhea 9

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024494.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	NM_024494.3	MANE Select	c.182+120G>C		intron	N/A	NP_078613.1
	WNT2B	NM_004185.4		c.126-5310G>C		intron	N/A	NP_004176.2
	WNT2B	NM_001291880.1		c.-94-5310G>C		intron	N/A	NP_001278809.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	ENST00000369684.5	TSL:1 MANE Select	c.182+120G>C		intron	N/A	ENSP00000358698.4
	WNT2B	ENST00000369686.9	TSL:1	c.126-5310G>C		intron	N/A	ENSP00000358700.4
	WNT2B	ENST00000256640.9	TSL:2	c.-94-5310G>C		intron	N/A	ENSP00000256640.5

Frequencies

GnomAD3 genomes AF: 0.269 AC: 40908 AN: 152068 Hom.: 6316 Cov.: 33

Gnomad AFR AF: 0.118

Gnomad AMI AF: 0.332

Gnomad AMR AF: 0.328

Gnomad ASJ AF: 0.305

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.251

Gnomad FIN AF: 0.412

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.319 AC: 314586 AN: 987092 Hom.: 51140 AF XY: 0.317 AC XY: 155554 AN XY: 491346

African (AFR) AF: 0.114 AC: 2299 AN: 20248

American (AMR) AF: 0.351 AC: 3904 AN: 11124

Ashkenazi Jewish (ASJ) AF: 0.304 AC: 5464 AN: 18000

East Asian (EAS) AF: 0.462 AC: 13157 AN: 28482

South Asian (SAS) AF: 0.272 AC: 12849 AN: 47214

European-Finnish (FIN) AF: 0.416 AC: 12966 AN: 31200

Middle Eastern (MID) AF: 0.297 AC: 867 AN: 2916

European-Non Finnish (NFE) AF: 0.318 AC: 250103 AN: 785574

Other (OTH) AF: 0.307 AC: 12977 AN: 42334

GnomAD4 genome AF: 0.269 AC: 40906 AN: 152186 Hom.: 6316 Cov.: 33 AF XY: 0.276 AC XY: 20565 AN XY: 74382

African (AFR) AF: 0.118 AC: 4904 AN: 41540

American (AMR) AF: 0.328 AC: 5020 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.305 AC: 1058 AN: 3472

East Asian (EAS) AF: 0.435 AC: 2247 AN: 5166

South Asian (SAS) AF: 0.250 AC: 1207 AN: 4822

European-Finnish (FIN) AF: 0.412 AC: 4359 AN: 10578

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.311 AC: 21154 AN: 67988

Other (OTH) AF: 0.275 AC: 582 AN: 2114

Alfa AF: 0.285 Hom.: 902

Bravo AF: 0.260

Asia WGS AF: 0.318 AC: 1101 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	9.1
DANN	Benign	0.65
PhyloP100		1.9
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: rs3790606; hg19: chr1-113052186; COSMIC: COSV56673250;