Variant 6-117271038-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_182645.3(VGLL2):c.887A>G(p.Gln296Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000926 in 1,080,228 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: not found (cov: 31)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

VGLL2
NM_182645.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.884

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13185349).

BS2

High AC in GnomAdExome4 at 10 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
VGLL2	NM_182645.3 linkuse as main transcript	c.887A>G	p.Gln296Arg	missense_variant	3/4	ENST00000326274.6	NP_872586.1
VGLL2	XM_005266883.3 linkuse as main transcript	c.887A>G	p.Gln296Arg	missense_variant	3/4		XP_005266940.1
VGLL2	NM_153453.1 linkuse as main transcript	c.392-1416A>G		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.887A>G	p.Gln296Arg	missense_variant	3/4	1	NM_182645.3	ENSP00000320957	P4	Q8N8G2-1
VGLL2	ENST00000352536.7 linkuse as main transcript	c.392-1416A>G		intron_variant		1		ENSP00000305405	A1	Q8N8G2-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000926

AC:

AN:

1080228

Hom.:

Cov.:

AF XY:

0.00000586

AC XY:

AN XY:

512126

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 16, 2024

The c.887A>G (p.Q296R) alteration is located in exon 3 (coding exon 3) of the VGLL2 gene. This alteration results from a A to G substitution at nucleotide position 887, causing the glutamine (Q) at amino acid position 296 to be replaced by an arginine (R). 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

0.13

BayesDel_addAF

Benign

-0.088

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.068

Eigen

Benign

-0.27

Eigen_PC

Benign

-0.17

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.60

M_CAP

Benign

0.033

MetaRNN

Benign

0.13

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

D;N

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.85

REVEL

Benign

0.13

Sift

Benign

0.081

Sift4G

Benign

0.26

Polyphen

0.084

Vest4

0.11

MutPred

0.16

Gain of methylation at Q296 (P = 0.028);

MVP

0.56

MPC

0.54

ClinPred

0.36

GERP RS

3.1

Varity_R

0.099

gMVP

0.45

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over