Variant 11-124749752-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014312.5(VSIG2):c.542G>A(p.Arg181His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000239 in 1,613,656 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00017 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00025 ( 1 hom. )

Consequence

VSIG2
NM_014312.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.56

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051653445).

BP6

Variant 11-124749752-C-T is Benign according to our data. Variant chr11-124749752-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2588754.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
VSIG2	NM_014312.5 linkuse as main transcript	c.542G>A	p.Arg181His	missense_variant	4/7	ENST00000326621.10	NP_055127.2	Q96IQ7-1
VSIG2	NM_001329920.2 linkuse as main transcript	c.542G>A	p.Arg181His	missense_variant	4/6		NP_001316849.1	Q96IQ7-2
VSIG2	XM_047426684.1 linkuse as main transcript	c.542G>A	p.Arg181His	missense_variant	4/5		XP_047282640.1
VSIG2	XM_047426685.1 linkuse as main transcript	c.176G>A	p.Arg59His	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.542G>A	p.Arg181His	missense_variant	4/7	1	NM_014312.5	ENSP00000318684.5		Q96IQ7-1
VSIG2	ENST00000403470.1 linkuse as main transcript	c.542G>A	p.Arg181His	missense_variant	4/6	2		ENSP00000385013.1		Q96IQ7-2

Frequencies

GnomAD3 genomes

AF:

0.000165

AC:

AN:

151752

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000727

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000231

AC:

AN:

251338

Hom.:

AF XY:

0.000228

AC XY:

AN XY:

135864

show subpopulations

Gnomad AFR exome

AF:

0.0000615

Gnomad AMR exome

AF:

0.000260

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000352

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000246

AC:

360

AN:

1461790

Hom.:

Cov.:

AF XY:

0.000241

AC XY:

175

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.000149

Gnomad4 AMR exome

AF:

0.000268

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.000174

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000275

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000171

AC:

AN:

151866

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74254

show subpopulations

Gnomad4 AFR

AF:

0.0000725

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000297

Hom.:

Bravo

AF:

0.000193

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000214

AC:

EpiCase

AF:

0.000600

EpiControl

AF:

0.000534

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.76

CADD

Benign

1.3

DANN

Benign

0.95

DEOGEN2

Benign

0.11

T;.

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.99

FATHMM_MKL

Benign

0.024

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.0045

MetaRNN

Benign

0.052

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;L

PrimateAI

Benign

0.23

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.031

Sift

Benign

0.17

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0090

B;.

Vest4

0.28

MVP

0.040

MPC

0.047

ClinPred

0.017

GERP RS

-2.0

Varity_R

0.047

gMVP

0.44

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