Genetic Variant NM_006522.4:c.427C>G (chr2-218871610-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_006522.4(WNT6):c.427C>G(p.Pro143Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000015 in 1,334,838 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000015 ( 0 hom. )

Consequence

WNT6
NM_006522.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.34

Publications

0 publications found

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]

WNT6 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41197187).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006522.4. 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
	WNT6	NM_006522.4	MANE Select	c.427C>G	p.Pro143Ala	missense	Exon 3 of 4	NP_006513.1	Q9Y6F9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT6	ENST00000233948.4	TSL:1 MANE Select	c.427C>G	p.Pro143Ala	missense	Exon 3 of 4	ENSP00000233948.3	Q9Y6F9
	WNT6	ENST00000486233.1	TSL:5	n.279C>G		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000106

AC:

AN:

94448

AF XY:

0.00

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000654

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000150

AC:

AN:

1334838

Hom.:

Cov.:

AF XY:

0.00000152

AC XY:

AN XY:

657560

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27378

American (AMR)

AF:

0.0000748

AC:

AN:

26750

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21648

East Asian (EAS)

AF:

0.00

AC:

AN:

30812

South Asian (SAS)

AF:

0.00

AC:

AN:

70206

European-Finnish (FIN)

AF:

0.00

AC:

AN:

41690

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4098

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1057208

Other (OTH)

AF:

0.00

AC:

AN:

55048

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Uncertain

0.42

Eigen

Benign

-0.22

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.68

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.41

MetaSVM

Benign

-0.81

MutationAssessor

Benign

1.5

PhyloP100

3.3

PrimateAI

Uncertain

0.70

PROVEAN

Benign

-1.2

REVEL

Benign

0.19

Sift

Benign

0.48

Sift4G

Benign

0.47

Polyphen

0.91

Vest4

0.27

MutPred

0.37

Loss of glycosylation at P143 (P = 0.0143)

MVP

0.74

MPC

0.61

ClinPred

0.15

GERP RS

3.6

Varity_R

0.061

gMVP

0.41

Mutation Taster

=79/21

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over