6-117268457-C-A

Position:

• chr6-117268457-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000326274.6(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. 13/21 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 ENST00000326274.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.45

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VGLL2	NM_182645.3	c.357C>A	p.Ser119Arg	missense_variant	2/4	ENST00000326274.6	NP_872586.1
VGLL2	NM_153453.1	c.357C>A	p.Ser119Arg	missense_variant	2/3		NP_703154.1
VGLL2	XM_005266883.3	c.357C>A	p.Ser119Arg	missense_variant	2/4		XP_005266940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VGLL2	ENST00000326274.6	c.357C>A	p.Ser119Arg	missense_variant	2/4	1	NM_182645.3	ENSP00000320957.5
VGLL2	ENST00000352536.7	c.357C>A	p.Ser119Arg	missense_variant	2/3	1		ENSP00000305405.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 22, 2024

The c.357C>A (p.S119R) alteration is located in exon 2 (coding exon 2) of the VGLL2 gene. This alteration results from a C to A substitution at nucleotide position 357, causing the serine (S) at amino acid position 119 to be replaced by an arginine (R). 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	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;T
M_CAP	Benign	0.0097	T
MetaRNN	Benign	0.22	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.15
Sift	Benign	0.37	T;T
Sift4G	Benign	0.20	T;T
Polyphen		0.81	P;P
Vest4		0.45
MutPred		0.22		Loss of phosphorylation at S119 (P = 0.0087);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

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr6-117589620;