Genetic Variant NM_006522.4:c.448G>A (chr2-218871631-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006522.4(WNT6):c.448G>A(p.Gly150Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000152 in 1,320,094 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G150R) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

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: 0.644

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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.448G>A	p.Gly150Ser	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.448G>A	p.Gly150Ser	missense	Exon 3 of 4	ENSP00000233948.3	Q9Y6F9
	WNT6	ENST00000486233.1	TSL:5	n.300G>A		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000152

AC:

AN:

1320094

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

648320

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26908

American (AMR)

AF:

0.00

AC:

AN:

24408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20336

East Asian (EAS)

AF:

0.00

AC:

AN:

30306

South Asian (SAS)

AF:

0.00

AC:

AN:

67218

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3940

European-Non Finnish (NFE)

AF:

0.00000191

AC:

AN:

1049406

Other (OTH)

AF:

0.00

AC:

AN:

54300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

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

0.096

BayesDel_addAF

Benign

-0.020

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.37

Eigen

Benign

-0.017

Eigen_PC

Benign

-0.059

FATHMM_MKL

Benign

0.76

LIST_S2

Benign

0.72

M_CAP

Pathogenic

0.85

MetaRNN

Uncertain

0.48

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.55

PhyloP100

0.64

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.14

REVEL

Uncertain

0.40

Sift

Benign

0.41

Sift4G

Benign

0.26

Polyphen

1.0

Vest4

0.25

MutPred

0.41

Gain of glycosylation at G150 (P = 0)

MVP

0.82

MPC

0.75

ClinPred

0.37

GERP RS

4.0

Varity_R

0.096

gMVP

0.34

Mutation Taster

=78/22

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over