Variant 6-117271023-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_182645.3(VGLL2):c.872C>T(p.Ser291Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00042 in 1,232,248 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00045 ( 0 hom. )

Consequence

VGLL2
NM_182645.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.97

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.054599583).

BS2

High AC in GnomAd4 at 33 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VGLL2	NM_182645.3 linkuse as main transcript	c.872C>T	p.Ser291Leu	missense_variant	3/4	ENST00000326274.6	NP_872586.1
VGLL2	XM_005266883.3 linkuse as main transcript	c.872C>T	p.Ser291Leu	missense_variant	3/4		XP_005266940.1
VGLL2	NM_153453.1 linkuse as main transcript	c.392-1431C>T		intron_variant			NP_703154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL2	ENST00000326274.6 linkuse as main transcript	c.872C>T	p.Ser291Leu	missense_variant	3/4	1	NM_182645.3	ENSP00000320957	P4	Q8N8G2-1
VGLL2	ENST00000352536.7 linkuse as main transcript	c.392-1431C>T		intron_variant		1		ENSP00000305405	A1	Q8N8G2-2

Frequencies

GnomAD3 genomes

AF:

0.000218

AC:

AN:

151070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000726

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000659

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000195

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000251

Gnomad OTH

AF:

0.000481

GnomAD4 exome

AF:

0.000448

AC:

484

AN:

1081178

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

235

AN XY:

512680

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000481

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000490

Gnomad4 OTH exome

AF:

0.000531

GnomAD4 genome

AF:

0.000218

AC:

AN:

151070

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

AN XY:

73746

show subpopulations

Gnomad4 AFR

AF:

0.0000726

Gnomad4 AMR

AF:

0.000659

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000195

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000251

Gnomad4 OTH

AF:

0.000481

Alfa

AF:

0.000485

Hom.:

Bravo

AF:

0.000321

ExAC

AF:

0.0000858

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 20, 2021

The c.872C>T (p.S291L) alteration is located in exon 3 (coding exon 3) of the VGLL2 gene. This alteration results from a C to T substitution at nucleotide position 872, causing the serine (S) at amino acid position 291 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.098

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.017

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.43

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.79

M_CAP

Benign

0.040

MetaRNN

Benign

0.055

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.14

MutationTaster

Benign

0.95

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.74

REVEL

Benign

0.092

Sift

Benign

0.066

Sift4G

Uncertain

0.052

Polyphen

0.012

Vest4

0.082

MVP

0.093

MPC

0.41

ClinPred

0.64

GERP RS

4.5

Varity_R

0.15

gMVP

0.21

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

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