Variant 6-117270618-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000326274.6(VGLL2):c.467C>A(p.Pro156Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000438 in 1,592,574 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 0.00068 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00041 ( 10 hom. )

Consequence

VGLL2
ENST00000326274.6 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.69

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028758645).

BP6

Variant 6-117270618-C-A is Benign according to our data. Variant chr6-117270618-C-A is described in ClinVar as [Benign]. Clinvar id is 731356.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 103 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL2	NM_182645.3 linkuse as main transcript	c.467C>A	p.Pro156Gln	missense_variant	3/4	ENST00000326274.6	NP_872586.1	Q8N8G2-1
VGLL2	XM_005266883.3 linkuse as main transcript	c.467C>A	p.Pro156Gln	missense_variant	3/4		XP_005266940.1
VGLL2	NM_153453.1 linkuse as main transcript	c.392-1836C>A		intron_variant			NP_703154.1	Q8N8G2-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL2	ENST00000326274.6 linkuse as main transcript	c.467C>A	p.Pro156Gln	missense_variant	3/4	1	NM_182645.3	ENSP00000320957.5		Q8N8G2-1
VGLL2	ENST00000352536.7 linkuse as main transcript	c.392-1836C>A		intron_variant		1		ENSP00000305405.5		Q8N8G2-2

Frequencies

GnomAD3 genomes

AF:

0.000677

AC:

103

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0174

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00430

GnomAD3 exomes

AF:

0.00141

AC:

297

AN:

211270

Hom.:

AF XY:

0.00119

AC XY:

139

AN XY:

117228

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000304

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0182

Gnomad SAS exome

AF:

0.000107

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000567

GnomAD4 exome

AF:

0.000413

AC:

595

AN:

1440308

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

270

AN XY:

715988

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000229

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0133

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.00126

GnomAD4 genome

AF:

0.000676

AC:

103

AN:

152266

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0174

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0000225

Hom.:

Bravo

AF:

0.000759

ExAC

AF:

0.00122

AC:

145

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

0.091

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.59

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.053

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.62

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.61

PROVEAN

Benign

-1.1

REVEL

Benign

0.063

Sift

Uncertain

0.010

Sift4G

Benign

0.16

Polyphen

0.0

Vest4

0.14

MVP

0.082

MPC

0.47

ClinPred

0.066

GERP RS

4.3

Varity_R

0.11

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