chr6-117268457-C-A

Variant names:

• chr6-117268457-C-A
• NM_182645.3:c.357C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_182645.3(VGLL2):​c.357C>A​(p.Ser119Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: VGLL2 NM_182645.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.21809497).

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.357C>A	p.Ser119Arg	missense	Exon 2 of 4	NP_872586.1	Q8N8G2-1
	VGLL2	NM_153453.1		c.357C>A	p.Ser119Arg	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.357C>A	p.Ser119Arg	missense	Exon 2 of 4	ENSP00000320957.5	Q8N8G2-1
	VGLL2	ENST00000352536.7	TSL:1	c.357C>A	p.Ser119Arg	missense	Exon 2 of 3	ENSP00000305405.5	Q8N8G2-2
	VGLL2	ENST00000963224.1		c.330C>A	p.Ser110Arg	missense	Exon 2 of 4	ENSP00000633283.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.64
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.044	T
Eigen	Benign	-0.062
Eigen_PC	Benign	-0.058
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.22	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N
REVEL	Benign	0.15
Sift	Benign	0.37	T
Sift4G	Benign	0.20	T
Polyphen		0.81	P
Vest4		0.45
MutPred		0.22		Loss of phosphorylation at S119 (P = 0.0087)
MVP		0.18
MPC		1.2
ClinPred		0.67	D
GERP RS		4.3
Varity_R		0.11
gMVP		0.33
Mutation Taster		=60/40	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

hg19: chr6-117589620;