Genetic Variant VGLL2:p.His198Gln (chr6-117270745-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_182645.3(VGLL2):c.594C>G(p.His198Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,512,286 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

VGLL2
NM_182645.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.761

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 7 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182645.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL2	NM_182645.3	MANE Select	c.594C>G	p.His198Gln	missense	Exon 3 of 4	NP_872586.1	Q8N8G2-1
	VGLL2	NM_153453.1		c.392-1709C>G		intron	N/A	NP_703154.1	Q8N8G2-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
VGLL2	ENST00000326274.6	TSL:1 MANE Select	c.594C>G	p.His198Gln	missense	Exon 3 of 4	ENSP00000320957.5	Q8N8G2-1
VGLL2	ENST00000352536.7	TSL:1	c.392-1709C>G		intron	N/A	ENSP00000305405.5	Q8N8G2-2
VGLL2	ENST00000963224.1		c.567C>G	p.His189Gln	missense	Exon 3 of 4	ENSP00000633283.1

Frequencies

GnomAD3 genomes

AF:

0.0000462

AC:

AN:

151468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000737

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000872

AC:

AN:

114668

AF XY:

0.0000154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000213

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1360818

Hom.:

Cov.:

AF XY:

0.0000104

AC XY:

AN XY:

672838

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27758

American (AMR)

AF:

0.00

AC:

AN:

33394

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23640

East Asian (EAS)

AF:

0.00

AC:

AN:

31862

South Asian (SAS)

AF:

0.00

AC:

AN:

77004

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33950

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4204

European-Non Finnish (NFE)

AF:

0.0000159

AC:

AN:

1072472

Other (OTH)

AF:

0.0000177

AC:

AN:

56534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000462

AC:

AN:

151468

Hom.:

Cov.:

AF XY:

0.0000406

AC XY:

AN XY:

73960

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41314

American (AMR)

AF:

0.00

AC:

AN:

15186

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5120

South Asian (SAS)

AF:

0.00

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10454

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000737

AC:

AN:

67820

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000680

ExAC

AF:

0.0000301

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.34

BayesDel_addAF

Uncertain

0.019

BayesDel_noAF

Benign

-0.21

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.21

Eigen

Benign

0.17

Eigen_PC

Benign

0.095

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.63

M_CAP

Uncertain

0.18

MetaRNN

Uncertain

0.53

MetaSVM

Benign

-0.98

MutationAssessor

Uncertain

2.2

PhyloP100

0.76

PrimateAI

Pathogenic

0.93

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.15

Sift

Benign

0.21

Sift4G

Uncertain

0.015

Polyphen

1.0

Vest4

0.58

MutPred

0.18

Gain of catalytic residue at H198 (P = 0.1132)

MVP

0.33

MPC

1.3

ClinPred

0.97

GERP RS

3.5

Varity_R

0.37

gMVP

0.49

Mutation Taster

=55/45

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over