Genetic Variant VSIG2:p.Ile203Thr (chr11-124748742-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_014312.5(VSIG2):c.608T>C(p.Ile203Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,461,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

VSIG2
NM_014312.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2454735).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VSIG2	NM_014312.5 link	c.608T>C	p.Ile203Thr	missense_variant	Exon 5 of 7	ENST00000326621.10	NP_055127.2	Q96IQ7-1
VSIG2	NM_001329920.2 link	c.608T>C	p.Ile203Thr	missense_variant	Exon 5 of 6		NP_001316849.1	Q96IQ7-2
VSIG2	XM_047426685.1 link	c.242T>C	p.Ile81Thr	missense_variant	Exon 3 of 5		XP_047282641.1
VSIG2	XM_047426684.1 link	c.*18T>C		3_prime_UTR_variant	Exon 5 of 5		XP_047282640.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VSIG2	ENST00000326621.10 link	c.608T>C	p.Ile203Thr	missense_variant	Exon 5 of 7	1	NM_014312.5	ENSP00000318684.5		Q96IQ7-1
VSIG2	ENST00000403470.1 link	c.608T>C	p.Ile203Thr	missense_variant	Exon 5 of 6	2		ENSP00000385013.1		Q96IQ7-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461880

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727240

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39696

South Asian (SAS)

AF:

0.00

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000171

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 23, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.608T>C (p.I203T) alteration is located in exon 5 (coding exon 5) of the VSIG2 gene. This alteration results from a T to C substitution at nucleotide position 608, causing the isoleucine (I) at amino acid position 203 to be replaced by a threonine (T). 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

Uncertain

0.55

BayesDel_addAF

Benign

-0.079

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.20

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.70

T;T

M_CAP

Benign

0.017

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.015

N;N

PhyloP100

1.5

PrimateAI

Uncertain

0.65

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.080

Sift

Benign

0.031

D;D

Sift4G

Benign

0.40

T;T

Polyphen

0.0060

B;.

Vest4

0.40

MutPred

0.48

Gain of disorder (P = 0.0043);Gain of disorder (P = 0.0043);

MVP

0.25

MPC

0.25

ClinPred

0.69

GERP RS

4.3

Varity_R

0.15

gMVP

0.49

Mutation Taster

=80/20

polymorphism

(source)

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

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11-124748742-A-G

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over