2-218860595-C-G

Position:

• chr2-218860595-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006522.4(WNT6):​c.80+478C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 152,008 control chromosomes in the GnomAD database, including 14,204 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.35 (14204 hom., cov: 31)
• Consequence: WNT6 NM_006522.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.658

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WNT6	NM_006522.4	c.80+478C>G		intron_variant		ENST00000233948.4	NP_006513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WNT6	ENST00000233948.4	c.80+478C>G		intron_variant		1	NM_006522.4	ENSP00000233948.3
WNT6	ENST00000486233.1	n.153+478C>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.345 AC: 52454 AN: 151890 Hom.: 14155 Cov.: 31

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.393

Gnomad SAS AF: 0.274

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.310

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.346 AC: 52561 AN: 152008 Hom.: 14204 Cov.: 31 AF XY: 0.343 AC XY: 25487 AN XY: 74302

Gnomad4 AFR AF: 0.754

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.393

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.316

Alfa AF: 0.249 Hom.: 1092

Bravo AF: 0.370

Asia WGS AF: 0.402 AC: 1394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	11
DANN	Benign	0.72

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: rs6747776; hg19: chr2-219725318;