1-160419114-A-G

Position:

• chr1-160419114-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_020335.3(VANGL2):​c.305A>G​(p.Asp102Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: VANGL2 NM_020335.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.91

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VANGL2	NM_020335.3	c.305A>G	p.Asp102Gly	missense_variant	4/8	ENST00000368061.3	NP_065068.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VANGL2	ENST00000368061.3	c.305A>G	p.Asp102Gly	missense_variant	4/8	2	NM_020335.3	ENSP00000357040.2
VANGL2	ENST00000696602.1	c.449A>G	p.Asp150Gly	missense_variant	4/8			ENSP00000512747.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Dec 01, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.32	T
Eigen	Uncertain	0.23
Eigen_PC	Uncertain	0.27
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.046	D
MetaRNN	Uncertain	0.53	D
MetaSVM	Benign	-0.76	T
MutationAssessor	Uncertain	2.2	M
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.35
Sift	Benign	0.39	T
Sift4G	Benign	0.49	T
Polyphen		0.87	P
Vest4		0.55
MutPred		0.52		Gain of catalytic residue at S104 (P = 0.0713);
MVP		0.15
MPC		0.70
ClinPred		0.72	D
GERP RS		3.4
Varity_R		0.16
gMVP		0.55

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-160388904;