NM_024494.3:c.54C>G

Variant names:

• chr1-112509316-C-G
• rs1298645625
• NM_024494.3:c.54C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 2P and 7B. PM2 BP4_Strong BP6_Moderate BP7

The NM_024494.3(WNT2B):​c.54C>G​(p.Ala18Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000705 in 1,419,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.0e-7 (0 hom.)
• Consequence: WNT2B NM_024494.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.00
• Publications: 0 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: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 1-112509316-C-G is Benign according to our data. Variant chr1-112509316-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2810135.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0 with no splicing effect.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	NM_024494.3	MANE Select	c.54C>G	p.Ala18Ala	synonymous	Exon 1 of 5	NP_078613.1	Q93097-1
	WNT2B	NM_004185.4		c.126-5558C>G		intron	N/A	NP_004176.2	Q93097-2
	WNT2B	NM_001291880.1		c.-94-5558C>G		intron	N/A	NP_001278809.1	Q93097

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT2B	ENST00000369684.5	TSL:1 MANE Select	c.54C>G	p.Ala18Ala	synonymous	Exon 1 of 5	ENSP00000358698.4	Q93097-1
	WNT2B	ENST00000369686.9	TSL:1	c.126-5558C>G		intron	N/A	ENSP00000358700.4	Q93097-2
	WNT2B	ENST00000870348.1		c.54C>G	p.Ala18Ala	synonymous	Exon 1 of 5	ENSP00000540407.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000551 AC: 1 AN: 181644 AF XY: 0.00000987

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000127

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.05e-7 AC: 1 AN: 1419048 Hom.: 0 Cov.: 32 AF XY: 0.00000142 AC XY: 1 AN XY: 704270

African (AFR) AF: 0.00 AC: 0 AN: 31282

American (AMR) AF: 0.00 AC: 0 AN: 39426

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25266

East Asian (EAS) AF: 0.00 AC: 0 AN: 37852

South Asian (SAS) AF: 0.00 AC: 0 AN: 83006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 42150

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4104

European-Non Finnish (NFE) AF: 9.11e-7 AC: 1 AN: 1097106

Other (OTH) AF: 0.00 AC: 0 AN: 58856

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	9.9
DANN	Benign	0.69
PhyloP100		0.0
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism

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: rs1298645625; hg19: chr1-113051938;