6-117270890-G-A

Variant summary

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

The NM_182645.3(VGLL2):​c.739G>A​(p.Ala247Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000179 in 1,283,052 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000015 ( 0 hom. )

Consequence

VGLL2
NM_182645.3 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.37
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]

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=0.13803163).
BS2
High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
VGLL2NM_182645.3 linkuse as main transcriptc.739G>A p.Ala247Thr missense_variant 3/4 ENST00000326274.6 NP_872586.1
VGLL2XM_005266883.3 linkuse as main transcriptc.739G>A p.Ala247Thr missense_variant 3/4 XP_005266940.1
VGLL2NM_153453.1 linkuse as main transcriptc.392-1564G>A intron_variant NP_703154.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
VGLL2ENST00000326274.6 linkuse as main transcriptc.739G>A p.Ala247Thr missense_variant 3/41 NM_182645.3 ENSP00000320957 P4Q8N8G2-1
VGLL2ENST00000352536.7 linkuse as main transcriptc.392-1564G>A intron_variant 1 ENSP00000305405 A1Q8N8G2-2

Frequencies

GnomAD3 genomes
AF:
0.0000398
AC:
6
AN:
150888
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000121
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.0000984
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000150
AC:
17
AN:
1132164
Hom.:
0
Cov.:
31
AF XY:
0.0000164
AC XY:
9
AN XY:
548850
show subpopulations
Gnomad4 AFR exome
AF:
0.000175
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:
0.000248
Gnomad4 NFE exome
AF:
0.00000631
Gnomad4 OTH exome
AF:
0.0000223
GnomAD4 genome
AF:
0.0000398
AC:
6
AN:
150888
Hom.:
0
Cov.:
31
AF XY:
0.0000272
AC XY:
2
AN XY:
73664
show subpopulations
Gnomad4 AFR
AF:
0.000121
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.0000984
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000453

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 submitterclinical testingAmbry GeneticsDec 18, 2023The c.739G>A (p.A247T) alteration is located in exon 3 (coding exon 3) of the VGLL2 gene. This alteration results from a G to A substitution at nucleotide position 739, causing the alanine (A) at amino acid position 247 to be replaced by a threonine (T). 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
0.081
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
17
DANN
Uncertain
1.0
DEOGEN2
Benign
0.025
T
Eigen
Benign
0.088
Eigen_PC
Benign
0.051
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.65
T
M_CAP
Uncertain
0.16
D
MetaRNN
Benign
0.14
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.6
L
MutationTaster
Benign
1.0
D;D
PrimateAI
Pathogenic
0.90
D
PROVEAN
Benign
-0.55
N
REVEL
Benign
0.075
Sift
Benign
0.12
T
Sift4G
Uncertain
0.059
T
Polyphen
0.98
D
Vest4
0.12
MutPred
0.13
Gain of glycosylation at A247 (P = 0.0054);
MVP
0.093
MPC
0.45
ClinPred
0.82
D
GERP RS
3.9
Varity_R
0.10
gMVP
0.23

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.

Other links and lift over

dbSNP: rs1452661403; hg19: chr6-117592053; API