NM_006522.4:c.860C>T

Variant names:

• chr2-218873607-C-T
• rs1408841347
• NM_006522.4:c.860C>T

Variant summary

Our verdict is Likely benign. The variant received -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. 15/22 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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.79
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

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

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.860C>T	p.Ala287Val	missense	Exon 4 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.860C>T	p.Ala287Val	missense	Exon 4 of 4	ENSP00000233948.3	Q9Y6F9

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152236 Hom.: 0 Cov.: 32

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

African (AFR) AF: 0.00 AC: 0 AN: 31462

American (AMR) AF: 0.00 AC: 0 AN: 42060

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25418

East Asian (EAS) AF: 0.00 AC: 0 AN: 36284

South Asian (SAS) AF: 0.00 AC: 0 AN: 81564

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1092420

Other (OTH) AF: 0.0000512 AC: 3 AN: 58586

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152236 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74376

African (AFR) AF: 0.0000241 AC: 1 AN: 41464

American (AMR) AF: 0.000196 AC: 3 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5204

South Asian (SAS) AF: 0.00 AC: 0 AN: 4836

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000642

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

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
PhyloP100		1.8
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
Mutation Taster		=48/52	disease causing

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: rs1408841347; hg19: chr2-219738329;