Variant 11-124749715-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014312.5(VSIG2):c.579G>C(p.Met193Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

VSIG2
NM_014312.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.50

Variant links:

Genes affected

VSIG2 (HGNC:17149): (V-set and immunoglobulin domain containing 2) Predicted to be located in membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

VSIG2 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0992077).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG2	NM_014312.5 linkuse as main transcript	c.579G>C	p.Met193Ile	missense_variant	4/7	ENST00000326621.10	NP_055127.2	Q96IQ7-1
VSIG2	NM_001329920.2 linkuse as main transcript	c.579G>C	p.Met193Ile	missense_variant	4/6		NP_001316849.1	Q96IQ7-2
VSIG2	XM_047426684.1 linkuse as main transcript	c.579G>C	p.Met193Ile	missense_variant	4/5		XP_047282640.1
VSIG2	XM_047426685.1 linkuse as main transcript	c.213G>C	p.Met71Ile	missense_variant	2/5		XP_047282641.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
VSIG2	ENST00000326621.10 linkuse as main transcript	c.579G>C	p.Met193Ile	missense_variant	4/7	1	NM_014312.5	ENSP00000318684.5		Q96IQ7-1
VSIG2	ENST00000403470.1 linkuse as main transcript	c.579G>C	p.Met193Ile	missense_variant	4/6	2		ENSP00000385013.1		Q96IQ7-2

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000800

AC:

AN:

250012

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135176

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:

0.0000330

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000885

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000178

AC:

AN:

1460784

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726700

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:

0.0000225

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74340

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000151

ExAC

AF:

0.0000165

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

Sep 29, 2022

The c.579G>C (p.M193I) alteration is located in exon 4 (coding exon 4) of the VSIG2 gene. This alteration results from a G to C substitution at nucleotide position 579, causing the methionine (M) at amino acid position 193 to be replaced by an isoleucine (I). 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

0.23

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.023

T;.

Eigen

Benign

-0.21

Eigen_PC

Benign

-0.014

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.58

T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.099

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.56

N;N

PrimateAI

Benign

0.38

PROVEAN

Benign

-0.77

N;N

REVEL

Benign

0.094

Sift

Benign

0.16

T;T

Sift4G

Benign

0.38

T;T

Polyphen

0.0020

B;.

Vest4

0.35

MutPred

0.38

Gain of catalytic residue at M193 (P = 0.0024);Gain of catalytic residue at M193 (P = 0.0024);

MVP

0.31

MPC

0.045

ClinPred

0.27

GERP RS

4.6

Varity_R

0.16

gMVP

0.37

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