2-218873607-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_006522.4(WNT6):​c.860C>T​(p.Ala287Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000448 in 1,563,318 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

WNT6
NM_006522.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.79
Variant links:
Genes affected
WNT6 (HGNC:12785): (Wnt family member 6) 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. This gene is a member of the WNT gene family. It is overexpressed in cervical cancer cell line and strongly coexpressed with another family member, WNT10A, in colorectal cancer cell line. The gene overexpression may play key roles in carcinogenesis. This gene and the WNT10A gene are clustered in the chromosome 2q35 region. The protein encoded by this gene is 97% identical to the mouse Wnt6 protein at the amino acid level. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.24650466).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
WNT6NM_006522.4 linkc.860C>T p.Ala287Val missense_variant Exon 4 of 4 ENST00000233948.4 NP_006513.1 Q9Y6F9Q8N2E5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
WNT6ENST00000233948.4 linkc.860C>T p.Ala287Val missense_variant Exon 4 of 4 1 NM_006522.4 ENSP00000233948.3 Q9Y6F9

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152236
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.00000213
AC:
3
AN:
1411082
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
699450
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000512
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152236
Hom.:
0
Cov.:
32
AF XY:
0.0000269
AC XY:
2
AN XY:
74376
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000642

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jan 10, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.860C>T (p.A287V) alteration is located in exon 4 (coding exon 4) of the WNT6 gene. This alteration results from a C to T substitution at nucleotide position 860, causing the alanine (A) at amino acid position 287 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.043
T
BayesDel_noAF
Benign
-0.30
CADD
Benign
23
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.49
T
Eigen
Benign
-0.22
Eigen_PC
Benign
-0.096
FATHMM_MKL
Uncertain
0.78
D
LIST_S2
Uncertain
0.88
D
M_CAP
Benign
0.072
D
MetaRNN
Benign
0.25
T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
-0.14
N
PrimateAI
Pathogenic
0.82
D
PROVEAN
Benign
-1.2
N
REVEL
Benign
0.26
Sift
Benign
0.50
T
Sift4G
Benign
0.76
T
Polyphen
0.80
P
Vest4
0.089
MutPred
0.44
Loss of disorder (P = 0.1393);
MVP
0.51
MPC
1.7
ClinPred
0.94
D
GERP RS
4.3
Varity_R
0.25
gMVP
0.51

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1408841347; hg19: chr2-219738329; API