rs12086448

chr1-160424115-A-G

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_020335.3(VANGL2):c.1137A>G(p.Lys379=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.532 in 1,613,826 control chromosomes in the GnomAD database, including 231,884 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.58 (26727 hom., cov: 31)
  • Exomes 𝑓: 0.53 (205157 hom.)
• Consequence: VANGL2 NM_020335.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.12

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 1-160424115-A-G is Benign according to our data. Variant chr1-160424115-A-G is described in ClinVar as [Benign]. Clinvar id is 1684206.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL2	NM_020335.3	c.1137A>G	p.Lys379=	synonymous_variant	7/8	ENST00000368061.3
VANGL2	XM_005245357.2	c.1137A>G	p.Lys379=	synonymous_variant	8/9
VANGL2	XM_011509804.2	c.1137A>G	p.Lys379=	synonymous_variant	7/8
VANGL2	XM_047426020.1	c.1137A>G	p.Lys379=	synonymous_variant	7/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL2	ENST00000368061.3	c.1137A>G	p.Lys379=	synonymous_variant	7/8	2	NM_020335.3	P1
VANGL2	ENST00000696602.1	c.1281A>G	p.Lys427=	synonymous_variant	7/8
VANGL2	ENST00000483408.1	n.317A>G		non_coding_transcript_exon_variant	3/3	3

Frequencies

GnomAD3 genomes AF: 0.579 AC: 88005 AN: 151872 Hom.: 26713 Cov.: 31

Gnomad AFR AF: 0.764

Gnomad AMI AF: 0.591

Gnomad AMR AF: 0.489

Gnomad ASJ AF: 0.478

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.616

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.567

GnomAD3 exomes AF: 0.511 AC: 128496 AN: 251378 Hom.: 34050 AF XY: 0.516 AC XY: 70085 AN XY: 135862

Gnomad AFR exome AF: 0.768

Gnomad AMR exome AF: 0.380

Gnomad ASJ exome AF: 0.476

Gnomad EAS exome AF: 0.367

Gnomad SAS exome AF: 0.610

Gnomad FIN exome AF: 0.483

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.503

GnomAD4 exome AF: 0.527 AC: 769714 AN: 1461836 Hom.: 205157 Cov.: 82 AF XY: 0.528 AC XY: 383723 AN XY: 727214

Gnomad4 AFR exome AF: 0.773

Gnomad4 AMR exome AF: 0.399

Gnomad4 ASJ exome AF: 0.476

Gnomad4 EAS exome AF: 0.380

Gnomad4 SAS exome AF: 0.605

Gnomad4 FIN exome AF: 0.476

Gnomad4 NFE exome AF: 0.527

Gnomad4 OTH exome AF: 0.526

GnomAD4 genome AF: 0.579 AC: 88064 AN: 151990 Hom.: 26727 Cov.: 31 AF XY: 0.576 AC XY: 42778 AN XY: 74272

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.489

Gnomad4 ASJ AF: 0.478

Gnomad4 EAS AF: 0.375

Gnomad4 SAS AF: 0.615

Gnomad4 FIN AF: 0.482

Gnomad4 NFE AF: 0.521

Gnomad4 OTH AF: 0.565

Alfa AF: 0.545 Hom.: 17286

Bravo AF: 0.585

Asia WGS AF: 0.525 AC: 1824 AN: 3478

EpiCase AF: 0.528

EpiControl AF: 0.527

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Neural tube defect Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Dec 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	11
Dann	Benign	0.63

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12086448; hg19: chr1-160393905; COSMIC: COSV63604186;