Variant chr7-54546968-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001301009.2(VSTM2A):c.268G>A(p.Asp90Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000439 in 1,595,714 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

VSTM2A
NM_001301009.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.25

Variant links:

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]

VSTM2A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2A	NM_001301009.2 linkuse as main transcript	c.268G>A	p.Asp90Asn	missense_variant	3/5	ENST00000402613.4	NP_001287938.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSTM2A	ENST00000402613.4 linkuse as main transcript	c.268G>A	p.Asp90Asn	missense_variant	3/5	2	NM_001301009.2	ENSP00000384103	A1

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.00000416

AC:

AN:

1443766

Hom.:

Cov.:

AF XY:

0.00000418

AC XY:

AN XY:

718176

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000543

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000658

AC:

AN:

151948

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74208

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

ExAC

AF:

0.00000826

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 17, 2024

The c.268G>A (p.D90N) alteration is located in exon 3 (coding exon 3) of the VSTM2A gene. This alteration results from a G to A substitution at nucleotide position 268, causing the aspartic acid (D) at amino acid position 90 to be replaced by an asparagine (N). 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

Benign

0.14

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.49

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

.;T;.;T

Eigen

Benign

-0.012

Eigen_PC

Benign

-0.048

FATHMM_MKL

Uncertain

0.88

LIST_S2

Uncertain

0.91

D;D;D;D

M_CAP

Benign

0.076

MetaRNN

Uncertain

0.48

T;T;T;T

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.9

L;L;.;.

MutationTaster

Benign

0.96

D;D;D;D;D

PrimateAI

Uncertain

0.69

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.26

Sift

Benign

0.078

T;T;T;T

Sift4G

Benign

0.075

T;T;T;T

Polyphen

0.98

D;P;D;.

Vest4

0.49

MutPred

0.48

Loss of phosphorylation at S93 (P = 0.096);Loss of phosphorylation at S93 (P = 0.096);Loss of phosphorylation at S93 (P = 0.096);Loss of phosphorylation at S93 (P = 0.096);

MVP

0.38

MPC

0.61

ClinPred

0.91

GERP RS

3.6

Varity_R

0.18

gMVP

0.48

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over