rs68106607

Positions:

• chr7-54553999-G-A
• chr7-54553999-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301009.2(VSTM2A):​c.634+3829G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.126 in 1,552,980 control chromosomes in the GnomAD database, including 13,143 homozygotes. 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 0.13 (1438 hom., cov: 31)
  • Exomes 𝑓: 0.13 (11705 hom.)
• Consequence: VSTM2A NM_001301009.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.01

Genes affected

VSTM2A (HGNC:28499): (V-set and transmembrane domain containing 2A) Predicted to enable identical protein binding activity. Involved in several processes, including positive regulation of brown fat cell differentiation; positive regulation of lipid storage; and positive regulation of white fat cell proliferation. Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0044590235).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2A	NM_001301009.2	c.634+3829G>A		intron_variant		ENST00000402613.4	NP_001287938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2A	ENST00000402613.4	c.634+3829G>A		intron_variant		2	NM_001301009.2	ENSP00000384103	A1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19677 AN: 151904 Hom.: 1435 Cov.: 31

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.201

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.140

Gnomad EAS AF: 0.00155

Gnomad SAS AF: 0.0511

Gnomad FIN AF: 0.0972

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.137

GnomAD3 exomes AF: 0.101 AC: 15659 AN: 155492 Hom.: 956 AF XY: 0.100 AC XY: 8316 AN XY: 83102

Gnomad AFR exome AF: 0.151

Gnomad AMR exome AF: 0.0802

Gnomad ASJ exome AF: 0.127

Gnomad EAS exome AF: 0.000274

Gnomad SAS exome AF: 0.0580

Gnomad FIN exome AF: 0.0969

Gnomad NFE exome AF: 0.133

Gnomad OTH exome AF: 0.126

GnomAD4 exome AF: 0.125 AC: 175572 AN: 1400958 Hom.: 11705 Cov.: 36 AF XY: 0.124 AC XY: 85479 AN XY: 691116

Gnomad4 AFR exome AF: 0.150

Gnomad4 AMR exome AF: 0.0887

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.000307

Gnomad4 SAS exome AF: 0.0588

Gnomad4 FIN exome AF: 0.100

Gnomad4 NFE exome AF: 0.136

Gnomad4 OTH exome AF: 0.125

GnomAD4 genome AF: 0.130 AC: 19700 AN: 152022 Hom.: 1438 Cov.: 31 AF XY: 0.126 AC XY: 9325 AN XY: 74292

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.140

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0514

Gnomad4 FIN AF: 0.0972

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.136

Alfa AF: 0.120 Hom.: 733

Bravo AF: 0.135

TwinsUK AF: 0.141 AC: 523

ALSPAC AF: 0.127 AC: 488

ExAC AF: 0.0609 AC: 2255

Asia WGS AF: 0.0440 AC: 155 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.80	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.63
DANN	Benign	0.58
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.00074	N
LIST_S2	Benign	0.33	T
MetaRNN	Benign	0.0045	T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	P;P;P
PROVEAN	Benign	0.22	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.0010	B
Vest4		0.023
ClinPred		0.0015	T
GERP RS		0.32

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

LitVar

Other links and lift over

dbSNP: rs68106607; hg19: chr7-54621692; COSMIC: COSV105125802; COSMIC: COSV105125802;