1-160421119-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The NM_020335.3(VANGL2):c.1005C>T(p.Asp335=) variant causes a synonymous change. The variant allele was found at a frequency of 0.00105 in 1,614,056 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0056 (5 hom., cov: 32)
  • Exomes 𝑓: 0.00057 (7 hom.)
• Consequence: VANGL2 NM_020335.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 5.83

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.32).
• BP6: Variant 1-160421119-C-T is Benign according to our data. Variant chr1-160421119-C-T is described in ClinVar as [Benign]. Clinvar id is 720022.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0056 (853/152206) while in subpopulation AFR AF= 0.019 (789/41524). AF 95% confidence interval is 0.0179. There are 5 homozygotes in gnomad4. There are 430 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 851 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
VANGL2	NM_020335.3	c.1005C>T	p.Asp335=	synonymous_variant	6/8	ENST00000368061.3
VANGL2	XM_005245357.2	c.1005C>T	p.Asp335=	synonymous_variant	7/9
VANGL2	XM_011509804.2	c.1005C>T	p.Asp335=	synonymous_variant	6/8
VANGL2	XM_047426020.1	c.1005C>T	p.Asp335=	synonymous_variant	6/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
VANGL2	ENST00000368061.3	c.1005C>T	p.Asp335=	synonymous_variant	6/8	2	NM_020335.3	P1
VANGL2	ENST00000696602.1	c.1149C>T	p.Asp383=	synonymous_variant	6/8
VANGL2	ENST00000483408.1	n.185C>T		non_coding_transcript_exon_variant	2/3	3

Frequencies

GnomAD3 genomes AF: 0.00560 AC: 851 AN: 152090 Hom.: 5 Cov.: 32

Gnomad AFR AF: 0.0190

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00216

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.000850

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000176

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.00135 AC: 339 AN: 251360 Hom.: 2 AF XY: 0.00102 AC XY: 139 AN XY: 135868

Gnomad AFR exome AF: 0.0179

Gnomad AMR exome AF: 0.000636

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.000417

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.000977

GnomAD4 exome AF: 0.000573 AC: 838 AN: 1461850 Hom.: 7 Cov.: 32 AF XY: 0.000521 AC XY: 379 AN XY: 727228

Gnomad4 AFR exome AF: 0.0187

Gnomad4 AMR exome AF: 0.000626

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.000506

Gnomad4 NFE exome AF: 0.0000585

Gnomad4 OTH exome AF: 0.00129

GnomAD4 genome AF: 0.00560 AC: 853 AN: 152206 Hom.: 5 Cov.: 32 AF XY: 0.00578 AC XY: 430 AN XY: 74410

Gnomad4 AFR AF: 0.0190

Gnomad4 AMR AF: 0.00216

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.000850

Gnomad4 NFE AF: 0.000176

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00237 Hom.: 1

Bravo AF: 0.00574

Asia WGS AF: 0.00144 AC: 5 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 08, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.32
Cadd	Benign	12
Dann	Benign	0.94

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: rs140982917; hg19: chr1-160390909;