rs17380141

Variant names:

• chr1-160425213-G-A
• rs17380141
• NM_020335.3:c.1401G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_020335.3(VANGL2):​c.1401G>A​(p.Pro467Pro) 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
• Publications: 18 publications found

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]

VANGL2 Gene-Disease associations (from GenCC):

• neural tube defects, susceptibility to

  Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Laboratory for Molecular Medicine, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
VANGL2	NM_020335.3	c.1401G>A	p.Pro467Pro	synonymous_variant	Exon 8 of 8	ENST00000368061.3	NP_065068.1
VANGL2	XM_005245357.2	c.1401G>A	p.Pro467Pro	synonymous_variant	Exon 9 of 9		XP_005245414.1
VANGL2	XM_011509804.2	c.1401G>A	p.Pro467Pro	synonymous_variant	Exon 8 of 8		XP_011508106.1
VANGL2	XM_047426020.1	c.1401G>A	p.Pro467Pro	synonymous_variant	Exon 8 of 8		XP_047281976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VANGL2	ENST00000368061.3	c.1401G>A	p.Pro467Pro	synonymous_variant	Exon 8 of 8	2	NM_020335.3	ENSP00000357040.2
VANGL2	ENST00000696602.2	c.1545G>A	p.Pro515Pro	synonymous_variant	Exon 8 of 8			ENSP00000512747.1

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

GnomAD2 exomes AF: 0.253 AC: 63698 AN: 251294 AF XY: 0.261

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 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

African (AFR) AF: 0.231 AC: 7718 AN: 33480

American (AMR) AF: 0.213 AC: 9520 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 6685 AN: 26136

East Asian (EAS) AF: 0.0848 AC: 3368 AN: 39700

South Asian (SAS) AF: 0.293 AC: 25315 AN: 86254

European-Finnish (FIN) AF: 0.229 AC: 12246 AN: 53420

Middle Eastern (MID) AF: 0.302 AC: 1738 AN: 5764

European-Non Finnish (NFE) AF: 0.293 AC: 325911 AN: 1111990

Other (OTH) AF: 0.271 AC: 16392 AN: 60394

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

African (AFR) AF: 0.229 AC: 9505 AN: 41450

American (AMR) AF: 0.250 AC: 3817 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.260 AC: 902 AN: 3470

East Asian (EAS) AF: 0.0972 AC: 502 AN: 5166

South Asian (SAS) AF: 0.299 AC: 1438 AN: 4808

European-Finnish (FIN) AF: 0.227 AC: 2397 AN: 10542

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19645 AN: 67952

Other (OTH) AF: 0.276 AC: 580 AN: 2102

Alfa AF: 0.272 Hom.: 3805

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
PhyloP100		-0.19
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: rs17380141; hg19: chr1-160395003; COSMIC: COSV63604191; COSMIC: COSV63604191;