6-117268199-C-A

Variant names:

• chr6-117268199-C-A
• rs61746898
• NM_182645.3:c.99C>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_182645.3(VGLL2):​c.99C>A​(p.Ser33Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00538 in 1,613,724 control chromosomes in the GnomAD database, including 412 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (228 hom., cov: 32)
  • Exomes 𝑓: 0.0030 (184 hom.)
• Consequence: VGLL2 NM_182645.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.700
• Publications: 1 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.44).
• BP6: Variant 6-117268199-C-A is Benign according to our data. Variant chr6-117268199-C-A is described in ClinVar as Benign. ClinVar VariationId is 770557.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.7 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.097 is higher than 0.05.

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.99C>A	p.Ser33Ser	synonymous	Exon 2 of 4	NP_872586.1	Q8N8G2-1
	VGLL2	NM_153453.1		c.99C>A	p.Ser33Ser	synonymous	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.99C>A	p.Ser33Ser	synonymous	Exon 2 of 4	ENSP00000320957.5	Q8N8G2-1
	VGLL2	ENST00000352536.7	TSL:1	c.99C>A	p.Ser33Ser	synonymous	Exon 2 of 3	ENSP00000305405.5	Q8N8G2-2
	VGLL2	ENST00000963224.1		c.82-10C>A		intron	N/A	ENSP00000633283.1

Frequencies

GnomAD3 genomes AF: 0.0286 AC: 4344 AN: 152132 Hom.: 227 Cov.: 32

Gnomad AFR AF: 0.0996

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0105

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00712 AC: 1779 AN: 249932 AF XY: 0.00524

Gnomad AFR exome AF: 0.101

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000212

Gnomad OTH exome AF: 0.00329

GnomAD4 exome AF: 0.00296 AC: 4332 AN: 1461474 Hom.: 184 Cov.: 31 AF XY: 0.00258 AC XY: 1877 AN XY: 727078

African (AFR) AF: 0.104 AC: 3485 AN: 33380

American (AMR) AF: 0.00497 AC: 222 AN: 44646

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26108

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00608 AC: 35 AN: 5758

European-Non Finnish (NFE) AF: 0.000157 AC: 175 AN: 1111860

Other (OTH) AF: 0.00663 AC: 400 AN: 60356

GnomAD4 genome AF: 0.0286 AC: 4349 AN: 152250 Hom.: 228 Cov.: 32 AF XY: 0.0268 AC XY: 1994 AN XY: 74444

African (AFR) AF: 0.0995 AC: 4131 AN: 41518

American (AMR) AF: 0.0105 AC: 160 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000309 AC: 21 AN: 68018

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.0249 Hom.: 139

Bravo AF: 0.0327

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000178

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
BayesDel_noAF	Benign	-0.44
CADD	Benign	11
DANN	Benign	0.81
PhyloP100		0.70
Mutation Taster		=94/6	polymorphism (auto)

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: rs61746898; hg19: chr6-117589362;