2-218861775-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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 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 = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WNT6	NM_006522.4	c.80+1658T>C		intron_variant	Intron 1 of 3	ENST00000233948.4	NP_006513.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WNT6	ENST00000233948.4	c.80+1658T>C		intron_variant	Intron 1 of 3	1	NM_006522.4	ENSP00000233948.3
WNT6	ENST00000486233.1	n.153+1658T>C		intron_variant	Intron 1 of 1	5

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

Gnomad4 AFR AF: 0.746

Gnomad4 AMR AF: 0.284

Gnomad4 ASJ AF: 0.200

Gnomad4 EAS AF: 0.370

Gnomad4 SAS AF: 0.278

Gnomad4 FIN AF: 0.160

Gnomad4 NFE AF: 0.201

Gnomad4 OTH AF: 0.333

Alfa AF: 0.257 Hom.: 3270

Bravo AF: 0.389

Asia WGS AF: 0.382 AC: 1327 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	13
DANN	Benign	0.73

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: rs10193725; hg19: chr2-219726498;