6-117268482-C-G

Variant names:

• chr6-117268482-C-G
• rs147836127
• NM_182645.3:c.382C>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_182645.3(VGLL2):​c.382C>G​(p.Pro128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000917 in 1,607,720 control chromosomes in the GnomAD database, including 34 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0016 (3 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (31 hom.)
• Consequence: VGLL2 NM_182645.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.573
• Publications: 4 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0029548109).
• BP6: Variant 6-117268482-C-G is Benign according to our data. Variant chr6-117268482-C-G is described in ClinVar as Benign. ClinVar VariationId is 779915.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAd4 allele frequency = 0.00156 (238/152282) while in subpopulation EAS AF = 0.0323 (167/5164). AF 95% confidence interval is 0.0283. There are 3 homozygotes in GnomAd4. There are 119 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 238 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.382C>G	p.Pro128Ala	missense	Exon 2 of 4	NP_872586.1	Q8N8G2-1
	VGLL2	NM_153453.1		c.382C>G	p.Pro128Ala	missense	Exon 2 of 3	NP_703154.1	Q8N8G2-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VGLL2	ENST00000326274.6	TSL:1 MANE Select	c.382C>G	p.Pro128Ala	missense	Exon 2 of 4	ENSP00000320957.5	Q8N8G2-1
	VGLL2	ENST00000352536.7	TSL:1	c.382C>G	p.Pro128Ala	missense	Exon 2 of 3	ENSP00000305405.5	Q8N8G2-2
	VGLL2	ENST00000963224.1		c.355C>G	p.Pro119Ala	missense	Exon 2 of 4	ENSP00000633283.1

Frequencies

GnomAD3 genomes AF: 0.00156 AC: 238 AN: 152166 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000724

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00124

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0325

Gnomad SAS AF: 0.00228

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00478

GnomAD2 exomes AF: 0.00310 AC: 723 AN: 233154 AF XY: 0.00295

Gnomad AFR exome AF: 0.000742

Gnomad AMR exome AF: 0.000212

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0393

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00190

GnomAD4 exome AF: 0.000849 AC: 1236 AN: 1455438 Hom.: 31 Cov.: 31 AF XY: 0.000824 AC XY: 596 AN XY: 723588

African (AFR) AF: 0.000482 AC: 16 AN: 33228

American (AMR) AF: 0.000161 AC: 7 AN: 43566

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.0203 AC: 799 AN: 39352

South Asian (SAS) AF: 0.000990 AC: 85 AN: 85826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53144

Middle Eastern (MID) AF: 0.000184 AC: 1 AN: 5436

European-Non Finnish (NFE) AF: 0.0000171 AC: 19 AN: 1108762

Other (OTH) AF: 0.00514 AC: 309 AN: 60122

GnomAD4 genome AF: 0.00156 AC: 238 AN: 152282 Hom.: 3 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74468

African (AFR) AF: 0.000722 AC: 30 AN: 41566

American (AMR) AF: 0.00124 AC: 19 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.0323 AC: 167 AN: 5164

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00521 AC: 11 AN: 2112

Alfa AF: 0.00104 Hom.: 5

Bravo AF: 0.00196

ESP6500AA AF: 0.000455 AC: 2

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00243 AC: 294

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.97
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.44	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.57
PrimateAI	Benign	0.41	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.051
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.014	D
Polyphen		0.015	B
Vest4		0.27
MVP		0.082
MPC		0.45
ClinPred		0.0095	T
GERP RS		4.5
Varity_R		0.076
gMVP		0.25
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs147836127; hg19: chr6-117589645; COSMIC: COSV100409844;