chr7-54553999-G-A

Variant names:

• chr7-54553999-G-A
• rs68106607
• NM_001301009.2:c.634+3829G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001301009.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2A	NM_001301009.2	MANE Select	c.634+3829G>A		intron	N/A	NP_001287938.1
	VSTM2A	NM_182546.4		c.634+3829G>A		intron	N/A	NP_872352.2
	VSTM2A	NR_133927.2		n.444+3829G>A		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VSTM2A	ENST00000402613.4	TSL:2 MANE Select	c.634+3829G>A		intron	N/A	ENSP00000384103.3
	VSTM2A	ENST00000404951.5	TSL:5	c.767G>A	p.Arg256Gln	missense	Exon 5 of 6	ENSP00000384701.1
	VSTM2A	ENST00000407838.7	TSL:3	c.634+3829G>A		intron	N/A	ENSP00000384967.3

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

GnomAD2 exomes AF: 0.101 AC: 15659 AN: 155492 AF XY: 0.100

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 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

African (AFR) AF: 0.150 AC: 4735 AN: 31620

American (AMR) AF: 0.0887 AC: 3167 AN: 35710

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 3298 AN: 25182

East Asian (EAS) AF: 0.000307 AC: 11 AN: 35854

South Asian (SAS) AF: 0.0588 AC: 4661 AN: 79320

European-Finnish (FIN) AF: 0.100 AC: 4930 AN: 49212

Middle Eastern (MID) AF: 0.135 AC: 768 AN: 5704

European-Non Finnish (NFE) AF: 0.136 AC: 146725 AN: 1080058

Other (OTH) AF: 0.125 AC: 7277 AN: 58298

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

African (AFR) AF: 0.149 AC: 6182 AN: 41432

American (AMR) AF: 0.118 AC: 1810 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.140 AC: 486 AN: 3468

East Asian (EAS) AF: 0.00155 AC: 8 AN: 5160

South Asian (SAS) AF: 0.0514 AC: 247 AN: 4810

European-Finnish (FIN) AF: 0.0972 AC: 1026 AN: 10554

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.139 AC: 9430 AN: 68002

Other (OTH) AF: 0.136 AC: 286 AN: 2108

Alfa AF: 0.125 Hom.: 1217

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 v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
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
PhyloP100		-1.0
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
Mutation Taster		=100/0	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: rs68106607; hg19: chr7-54621692; COSMIC: COSV105125802; COSMIC: COSV105125802;