2-218861775-T-C

Variant names:

• chr2-218861775-T-C
• rs10193725
• NM_006522.4:c.80+1658T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006522.4(WNT6):​c.80+1658T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.365 in 151,942 control chromosomes in the GnomAD database, including 14,615 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 0.37 (14615 hom., cov: 31)
• Consequence: WNT6 NM_006522.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 9 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: Benign. The variant received -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 = 0.739 is higher than 0.05.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT6	NM_006522.4	MANE Select	c.80+1658T>C		intron	N/A	NP_006513.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WNT6	ENST00000233948.4	TSL:1 MANE Select	c.80+1658T>C		intron	N/A	ENSP00000233948.3
	WNT6	ENST00000486233.1	TSL:5	n.153+1658T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55410 AN: 151824 Hom.: 14562 Cov.: 31

Gnomad AFR AF: 0.746

Gnomad AMI AF: 0.218

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.160

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.329

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

GnomAD4 genome AF: 0.365 AC: 55516 AN: 151942 Hom.: 14615 Cov.: 31 AF XY: 0.361 AC XY: 26787 AN XY: 74262

African (AFR) AF: 0.746 AC: 30898 AN: 41392

American (AMR) AF: 0.284 AC: 4329 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 693 AN: 3462

East Asian (EAS) AF: 0.370 AC: 1912 AN: 5168

South Asian (SAS) AF: 0.278 AC: 1339 AN: 4808

European-Finnish (FIN) AF: 0.160 AC: 1696 AN: 10570

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13672 AN: 67974

Other (OTH) AF: 0.333 AC: 701 AN: 2104

Alfa AF: 0.270 Hom.: 5340

Bravo AF: 0.389

Asia WGS AF: 0.382 AC: 1327 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	13
DANN	Benign	0.73
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs10193725; hg19: chr2-219726498;