Variant 6-117268482-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The ENST00000326274.6(VGLL2):c.382C>G(p.Pro128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,607,720 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0016 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00085 ( 31 hom. )

Consequence

VGLL2
ENST00000326274.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.573

Variant links:

Genes affected

VGLL2 (HGNC:20232): (vestigial like family member 2) This gene encodes a protein with a transcriptional enhancer factor 1 (TEF-1) interaction domain. The encoded protein may act as a co-factor of TEF-1 regulated gene expression during skeletal muscle development. Alternatively spliced transcript variants encoding multiple isoforms have been observed. [provided by RefSeq, Jul 2012]

VGLL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0029548109).

BP6

Variant 6-117268482-C-G is Benign according to our data. Variant chr6-117268482-C-G is described in ClinVar as [Benign]. Clinvar id is 779915.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00156 (238/152282) while in subpopulation EAS AF= 0.0323 (167/5164). AF 95% confidence interval is 0.0283. There are 3 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 238 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL2	NM_182645.3 linkuse as main transcript	c.382C>G	p.Pro128Ala	missense_variant	2/4	ENST00000326274.6	NP_872586.1	Q8N8G2-1
VGLL2	NM_153453.1 linkuse as main transcript	c.382C>G	p.Pro128Ala	missense_variant	2/3		NP_703154.1	Q8N8G2-2
VGLL2	XM_005266883.3 linkuse as main transcript	c.382C>G	p.Pro128Ala	missense_variant	2/4		XP_005266940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL2	ENST00000326274.6 linkuse as main transcript	c.382C>G	p.Pro128Ala	missense_variant	2/4	1	NM_182645.3	ENSP00000320957.5		Q8N8G2-1
VGLL2	ENST00000352536.7 linkuse as main transcript	c.382C>G	p.Pro128Ala	missense_variant	2/3	1		ENSP00000305405.5		Q8N8G2-2

Frequencies

GnomAD3 genomes

AF:

0.00156

AC:

238

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00124

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0325

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00478

GnomAD3 exomes

AF:

0.00310

AC:

723

AN:

233154

Hom.:

AF XY:

0.00295

AC XY:

374

AN XY:

126574

show subpopulations

Gnomad AFR exome

AF:

0.000742

Gnomad AMR exome

AF:

0.000212

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0393

Gnomad SAS exome

AF:

0.000769

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00190

GnomAD4 exome

AF:

0.000849

AC:

1236

AN:

1455438

Hom.:

Cov.:

AF XY:

0.000824

AC XY:

596

AN XY:

723588

show subpopulations

Gnomad4 AFR exome

AF:

0.000482

Gnomad4 AMR exome

AF:

0.000161

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0203

Gnomad4 SAS exome

AF:

0.000990

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000171

Gnomad4 OTH exome

AF:

0.00514

GnomAD4 genome

AF:

0.00156

AC:

238

AN:

152282

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000722

Gnomad4 AMR

AF:

0.00124

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0323

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00104

Hom.:

Bravo

AF:

0.00196

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00243

AC:

294

Asia WGS

AF:

0.0240

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.038

.;T

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.44

LIST_S2

Benign

0.74

T;T

MetaRNN

Benign

0.0030

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

0.81

N;N

PrimateAI

Benign

0.41

PROVEAN

Uncertain

-2.7

D;N

REVEL

Benign

0.051

Sift

Uncertain

0.014

D;T

Sift4G

Uncertain

0.014

D;T

Polyphen

0.015

B;B

Vest4

0.27

MVP

0.082

MPC

0.45

ClinPred

0.0095

GERP RS

4.5

Varity_R

0.076

gMVP

0.25

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over