Genetic Variant VGLL2:p.His198His (chr6-117270745-C-T) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBP7BS2

The NM_182645.3(VGLL2):c.594C>T(p.His198His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000331 in 1,512,288 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000035 ( 0 hom. )

Consequence

VGLL2
NM_182645.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

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: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP7

Synonymous conserved (PhyloP=0.761 with no splicing effect.

BS2

High AC in GnomAdExome4 at 48 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>T	p.His198His	synonymous	Exon 3 of 4	NP_872586.1	Q8N8G2-1
	VGLL2	NM_153453.1		c.392-1709C>T		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>T	p.His198His	synonymous	Exon 3 of 4	ENSP00000320957.5	Q8N8G2-1
VGLL2	ENST00000352536.7	TSL:1	c.392-1709C>T		intron	N/A	ENSP00000305405.5	Q8N8G2-2
VGLL2	ENST00000963224.1		c.567C>T	p.His189His	synonymous	Exon 3 of 4	ENSP00000633283.1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000872

AC:

AN:

114668

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000353

AC:

AN:

1360820

Hom.:

Cov.:

AF XY:

0.0000416

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:

0.0000429

AC:

AN:

1072474

Other (OTH)

AF:

0.0000354

AC:

AN:

56534

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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:

0.0000132

AC:

AN:

151468

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73960

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

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:

0.0000295

AC:

AN:

67820

Other (OTH)

AF:

0.00

AC:

AN:

2082

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.400

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:

0.0000227

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

9.9

(source)

DANN

Benign

0.95

PhyloP100

0.76

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

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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