NM_006522.4:c.25C>A

Variant names:

• chr2-218860062-C-A
• rs1944292077
• NM_006522.4:c.25C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006522.4(WNT6):​c.25C>A​(p.Leu9Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WNT6 NM_006522.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2450245).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT6	NM_006522.4	c.25C>A	p.Leu9Ile	missense_variant	Exon 1 of 4	ENST00000233948.4	NP_006513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT6	ENST00000233948.4	c.25C>A	p.Leu9Ile	missense_variant	Exon 1 of 4	1	NM_006522.4	ENSP00000233948.3
WNT6	ENST00000486233.1	n.98C>A		non_coding_transcript_exon_variant	Exon 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1369274 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 675938

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: 0.00

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	14
DANN	Benign	0.93
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.96
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.29	T
M_CAP	Pathogenic	0.50	D
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	0.0	N
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-0.21	N
REVEL	Benign	0.16
Sift	Benign	0.30	T
Sift4G	Benign	0.22	T
Polyphen		0.78	P
Vest4		0.31
MutPred		0.45		Gain of catalytic residue at L14 (P = 0.0221);
MVP		0.33
MPC		2.0
ClinPred		0.080	T
GERP RS		1.6
Varity_R		0.055
gMVP		0.33

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

Other links and lift over

dbSNP: rs1944292077; hg19: chr2-219724785;