Variant 19-4292814-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_001169126.2(TMIGD2):c.622G>C(p.Glu208Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,462 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0000021 ( 0 hom. )

Consequence

TMIGD2
NM_001169126.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.761

Variant links:

Genes affected

TMIGD2 (HGNC:28324): (transmembrane and immunoglobulin domain containing 2) Enables coreceptor activity. Involved in positive regulation of T cell activation; positive regulation of angiogenesis; and positive regulation of cytokine production. Predicted to be located in plasma membrane. Predicted to be integral component of membrane. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

TMIGD2 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=0.08147389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIGD2	NM_001169126.2 linkuse as main transcript	c.622G>C	p.Glu208Gln	missense_variant	5/5	ENST00000595645.6	NP_001162597.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
TMIGD2	ENST00000595645.6 linkuse as main transcript	c.622G>C	p.Glu208Gln	missense_variant	5/5	1	NM_001169126.2	ENSP00000470561	A2	Q96BF3-2
TMIGD2	ENST00000301272.6 linkuse as main transcript	c.634G>C	p.Glu212Gln	missense_variant	5/5	1		ENSP00000301272	P2	Q96BF3-1
TMIGD2	ENST00000600114.5 linkuse as main transcript	c.274G>C	p.Glu92Gln	missense_variant	4/4	1		ENSP00000470494
TMIGD2	ENST00000600349.1 linkuse as main transcript	c.118G>C	p.Glu40Gln	missense_variant	2/2	1		ENSP00000471821

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000798

AC:

AN:

250774

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135702

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:

0.0000654

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461462

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727064

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:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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 29, 2024

The c.634G>C (p.E212Q) alteration is located in exon 5 (coding exon 5) of the TMIGD2 gene. This alteration results from a G to C substitution at nucleotide position 634, causing the glutamic acid (E) at amino acid position 212 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.71

CADD

Benign

0.96

DANN

Benign

0.84

DEOGEN2

Benign

0.0068

.;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.52

T;T;T;T

M_CAP

Benign

0.0074

MetaRNN

Benign

0.081

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.69

.;N;.;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.33

PROVEAN

Benign

-1.3

.;N;.;.

REVEL

Benign

0.038

Sift

Uncertain

0.020

.;D;.;.

Sift4G

Uncertain

0.040

D;D;T;T

Polyphen

0.076

B;B;.;.

Vest4

0.068

MutPred

0.083

.;Gain of methylation at K214 (P = 0.0853);.;.;

MVP

0.23

MPC

0.20

ClinPred

0.037

GERP RS

-1.8

Varity_R

0.049

gMVP

0.16

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