1-160425147-A-C

Position:

• chr1-160425147-A-C

Variant summary

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

The NM_020335.3(VANGL2):​c.1335A>C​(p.Gly445=) 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

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=-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/exons	MANE	UniProt
VANGL2	NM_020335.3	c.1335A>C	p.Gly445=	synonymous_variant	8/8	ENST00000368061.3
VANGL2	XM_005245357.2	c.1335A>C	p.Gly445=	synonymous_variant	9/9
VANGL2	XM_011509804.2	c.1335A>C	p.Gly445=	synonymous_variant	8/8
VANGL2	XM_047426020.1	c.1335A>C	p.Gly445=	synonymous_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL2	ENST00000368061.3	c.1335A>C	p.Gly445=	synonymous_variant	8/8	2	NM_020335.3	P1
VANGL2	ENST00000696602.1	c.1479A>C	p.Gly493=	synonymous_variant	8/8

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

GnomAD3 exomes AF: 0.249 AC: 62371 AN: 250968 Hom.: 8213 AF XY: 0.257 AC XY: 34930 AN XY: 135722

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 SAS exome AF: 0.293

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

Gnomad4 AFR exome AF: 0.161

Gnomad4 AMR exome AF: 0.209

Gnomad4 ASJ exome AF: 0.255

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: 0.267

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

Gnomad4 AFR AF: 0.164

Gnomad4 AMR AF: 0.243

Gnomad4 ASJ AF: 0.261

Gnomad4 EAS AF: 0.0976

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.227

Gnomad4 NFE AF: 0.289

Gnomad4 OTH AF: 0.260

Alfa AF: 0.276 Hom.: 8048

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

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: rs17380127; hg19: chr1-160394937; COSMIC: COSV63604426; COSMIC: COSV63604426;