rs17380127

Variant names:

• chr1-160425147-A-C
• rs17380127
• NM_020335.3:c.1335A>C

Your query was ambiguous. Multiple possible variants found:

• chr1-160425147-A-C
• chr1-160425147-A-G

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.1335A>C​(p.Gly445Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.274 in 1,613,818 control chromosomes in the GnomAD database, including 62,626 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 0.24 (4774 hom., cov: 31)
  • Exomes 𝑓: 0.28 (57852 hom.)
• Consequence: VANGL2 NM_020335.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.18
• Publications: 19 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=-1.18 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.287 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VANGL2	NM_020335.3	c.1335A>C	p.Gly445Gly	synonymous_variant	Exon 8 of 8	ENST00000368061.3	NP_065068.1
VANGL2	XM_005245357.2	c.1335A>C	p.Gly445Gly	synonymous_variant	Exon 9 of 9		XP_005245414.1
VANGL2	XM_011509804.2	c.1335A>C	p.Gly445Gly	synonymous_variant	Exon 8 of 8		XP_011508106.1
VANGL2	XM_047426020.1	c.1335A>C	p.Gly445Gly	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.1335A>C	p.Gly445Gly	synonymous_variant	Exon 8 of 8	2	NM_020335.3	ENSP00000357040.2
VANGL2	ENST00000696602.2	c.1479A>C	p.Gly493Gly	synonymous_variant	Exon 8 of 8			ENSP00000512747.1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36420 AN: 151894 Hom.: 4777 Cov.: 31

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.0974

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.294

Gnomad NFE AF: 0.289

Gnomad OTH AF: 0.261

GnomAD2 exomes AF: 0.249 AC: 62371 AN: 250968 AF XY: 0.257

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.203

Gnomad ASJ exome AF: 0.262

Gnomad EAS exome AF: 0.100

Gnomad FIN exome AF: 0.227

Gnomad NFE exome AF: 0.289

Gnomad OTH exome AF: 0.262

GnomAD4 exome AF: 0.278 AC: 406084 AN: 1461806 Hom.: 57852 Cov.: 49 AF XY: 0.279 AC XY: 202745 AN XY: 727198

African (AFR) AF: 0.161 AC: 5405 AN: 33476

American (AMR) AF: 0.209 AC: 9342 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 6655 AN: 26134

East Asian (EAS) AF: 0.0848 AC: 3367 AN: 39700

South Asian (SAS) AF: 0.293 AC: 25308 AN: 86252

European-Finnish (FIN) AF: 0.229 AC: 12246 AN: 53412

Middle Eastern (MID) AF: 0.291 AC: 1676 AN: 5768

European-Non Finnish (NFE) AF: 0.293 AC: 325979 AN: 1111964

Other (OTH) AF: 0.267 AC: 16106 AN: 60386

GnomAD4 genome AF: 0.240 AC: 36429 AN: 152012 Hom.: 4774 Cov.: 31 AF XY: 0.238 AC XY: 17702 AN XY: 74302

African (AFR) AF: 0.164 AC: 6799 AN: 41452

American (AMR) AF: 0.243 AC: 3716 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 904 AN: 3470

East Asian (EAS) AF: 0.0976 AC: 504 AN: 5164

South Asian (SAS) AF: 0.300 AC: 1446 AN: 4822

European-Finnish (FIN) AF: 0.227 AC: 2401 AN: 10568

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.289 AC: 19637 AN: 67940

Other (OTH) AF: 0.260 AC: 549 AN: 2112

Alfa AF: 0.271 Hom.: 10506

Bravo AF: 0.240

Asia WGS AF: 0.193 AC: 672 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	5.0
DANN	Benign	0.75
PhyloP100		-1.2
Mutation Taster		=98/2	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: rs17380127; hg19: chr1-160394937; COSMIC: COSV63604426; COSMIC: COSV63604426;