Variant 20-37944140-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000373461.9(VSTM2L):c.502A>G(p.Asn168Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,607,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 10/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 29)

Exomes 𝑓: 0.00031 ( 0 hom. )

Consequence

VSTM2L
ENST00000373461.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.22

Variant links:

Genes affected

VSTM2L (HGNC:16096): (V-set and transmembrane domain containing 2 like) Predicted to enable cell-cell adhesion mediator activity. Involved in negative regulation of neuron apoptotic process. Located in cytoplasm and extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

VSTM2L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.03234136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSTM2L	NM_080607.3 linkuse as main transcript	c.502A>G	p.Asn168Asp	missense_variant	4/4	ENST00000373461.9	NP_542174.1	Q96N03-1
VSTM2L	XM_011528530.2 linkuse as main transcript	c.451A>G	p.Asn151Asp	missense_variant	3/3		XP_011526832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
VSTM2L	ENST00000373461.9 linkuse as main transcript	c.502A>G	p.Asn168Asp	missense_variant	4/4	1	NM_080607.3	ENSP00000362560.4	Q96N03-1
VSTM2L	ENST00000373459.4 linkuse as main transcript	c.281A>G	p.Glu94Gly	missense_variant	2/2	3		ENSP00000362558.4	Q96N03-3
VSTM2L	ENST00000448944.1 linkuse as main transcript	c.*4A>G		downstream_gene_variant		3		ENSP00000406537.1	Q96N03-2

Frequencies

GnomAD3 genomes

AF:

0.000270

AC:

AN:

151878

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

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:

0.0000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000559

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000336

AC:

AN:

235218

Hom.:

AF XY:

0.000421

AC XY:

AN XY:

128400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000341

Gnomad FIN exome

AF:

0.000102

Gnomad NFE exome

AF:

0.000725

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000314

AC:

457

AN:

1455698

Hom.:

Cov.:

AF XY:

0.000304

AC XY:

220

AN XY:

723548

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000452

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.0000570

Gnomad4 NFE exome

AF:

0.000385

Gnomad4 OTH exome

AF:

0.000350

GnomAD4 genome

AF:

0.000270

AC:

AN:

151878

Hom.:

Cov.:

AF XY:

0.000229

AC XY:

AN XY:

74168

show subpopulations

Gnomad4 AFR

AF:

0.0000242

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000945

Gnomad4 NFE

AF:

0.000559

Gnomad4 OTH

AF:

0.000479

Alfa

AF:

0.000675

Hom.:

Bravo

AF:

0.000382

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000438

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Nov 07, 2022

The c.502A>G (p.N168D) alteration is located in exon 4 (coding exon 4) of the VSTM2L gene. This alteration results from a A to G substitution at nucleotide position 502, causing the asparagine (N) at amino acid position 168 to be replaced by an aspartic acid (D). 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

0.13

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.68

CADD

Uncertain

DANN

Uncertain

0.98

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.46

LIST_S2

Benign

0.29

M_CAP

Benign

0.050

MetaRNN

Benign

0.032

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.92

N;N;N

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.16

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Vest4

0.10

MVP

0.055

ClinPred

0.066

GERP RS

4.6

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