rs17380141

Positions:

• chr1-160425213-G-A

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020335.3(VANGL2):​c.1401G>A​(p.Pro467=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,824 control chromosomes in the GnomAD database, including 63,777 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 0.26 (5345 hom., cov: 31)
  • Exomes 𝑓: 0.28 (58432 hom.)
• Consequence: VANGL2 NM_020335.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.189

Genes affected

VANGL2 (HGNC:15511): (VANGL planar cell polarity protein 2) The protein encoded by this gene is a membrane protein involved in the regulation of planar cell polarity, especially in the stereociliary bundles of the cochlea. The encoded protein transmits directional signals to individual cells or groups of cells in epithelial sheets. This protein is also involved in the development of the neural plate. [provided by RefSeq, Sep 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=-0.189 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL2	NM_020335.3	c.1401G>A	p.Pro467=	synonymous_variant	8/8	ENST00000368061.3
VANGL2	XM_005245357.2	c.1401G>A	p.Pro467=	synonymous_variant	9/9
VANGL2	XM_011509804.2	c.1401G>A	p.Pro467=	synonymous_variant	8/8
VANGL2	XM_047426020.1	c.1401G>A	p.Pro467=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL2	ENST00000368061.3	c.1401G>A	p.Pro467=	synonymous_variant	8/8	2	NM_020335.3	P1
VANGL2	ENST00000696602.1	c.1545G>A	p.Pro515=	synonymous_variant	8/8

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39248 AN: 151848 Hom.: 5345 Cov.: 31

Gnomad AFR AF: 0.229

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.250

Gnomad ASJ AF: 0.260

Gnomad EAS AF: 0.0969

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.277

GnomAD3 exomes AF: 0.253 AC: 63698 AN: 251294 Hom.: 8490 AF XY: 0.261 AC XY: 35414 AN XY: 135812

Gnomad AFR exome AF: 0.233

Gnomad AMR exome AF: 0.206

Gnomad ASJ exome AF: 0.263

Gnomad EAS exome AF: 0.100

Gnomad SAS exome AF: 0.294

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.288

Gnomad OTH exome AF: 0.264

GnomAD4 exome AF: 0.280 AC: 408893 AN: 1461858 Hom.: 58432 Cov.: 52 AF XY: 0.280 AC XY: 203920 AN XY: 727224

Gnomad4 AFR exome AF: 0.231

Gnomad4 AMR exome AF: 0.213

Gnomad4 ASJ exome AF: 0.256

Gnomad4 EAS exome AF: 0.0848

Gnomad4 SAS exome AF: 0.293

Gnomad4 FIN exome AF: 0.229

Gnomad4 NFE exome AF: 0.293

Gnomad4 OTH exome AF: 0.271

GnomAD4 genome AF: 0.258 AC: 39266 AN: 151966 Hom.: 5345 Cov.: 31 AF XY: 0.256 AC XY: 19014 AN XY: 74270

Gnomad4 AFR AF: 0.229

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.260

Gnomad4 EAS AF: 0.0972

Gnomad4 SAS AF: 0.299

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.276

Alfa AF: 0.273 Hom.: 3027

Bravo AF: 0.261

Asia WGS AF: 0.199 AC: 692 AN: 3478

EpiCase AF: 0.304

EpiControl AF: 0.303

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.8
DANN	Benign	0.69

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: rs17380141; hg19: chr1-160395003; COSMIC: COSV63604191; COSMIC: COSV63604191;