Variant 19-4292689-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001169126.2(TMIGD2):c.747C>G(p.Gly249=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00228 in 1,603,166 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0013 ( 47 hom. )

Consequence

TMIGD2
NM_001169126.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.121

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 Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.95).

BP6

Variant 19-4292689-G-C is Benign according to our data. Variant chr19-4292689-G-C is described in ClinVar as [Benign]. Clinvar id is 786348.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.121 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0119 (1812/152162) while in subpopulation AFR AF= 0.0412 (1710/41530). AF 95% confidence interval is 0.0396. There are 37 homozygotes in gnomad4. There are 849 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
TMIGD2	NM_001169126.2 linkuse as main transcript	c.747C>G	p.Gly249=	synonymous_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.747C>G	p.Gly249=	synonymous_variant	5/5	1	NM_001169126.2	ENSP00000470561	A2	Q96BF3-2
TMIGD2	ENST00000301272.6 linkuse as main transcript	c.759C>G	p.Gly253=	synonymous_variant	5/5	1		ENSP00000301272	P2	Q96BF3-1
TMIGD2	ENST00000600114.5 linkuse as main transcript	c.399C>G	p.Gly133=	synonymous_variant	4/4	1		ENSP00000470494
TMIGD2	ENST00000600349.1 linkuse as main transcript	c.243C>G	p.Gly81=	synonymous_variant	2/2	1		ENSP00000471821

Frequencies

GnomAD3 genomes

AF:

0.0119

AC:

1807

AN:

152042

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0412

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.0139

GnomAD3 exomes

AF:

0.00311

AC:

747

AN:

239850

Hom.:

AF XY:

0.00227

AC XY:

297

AN XY:

130594

show subpopulations

Gnomad AFR exome

AF:

0.0426

Gnomad AMR exome

AF:

0.00170

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000102

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000192

Gnomad OTH exome

AF:

0.00242

GnomAD4 exome

AF:

0.00127

AC:

1849

AN:

1451004

Hom.:

Cov.:

AF XY:

0.00110

AC XY:

795

AN XY:

721638

show subpopulations

Gnomad4 AFR exome

AF:

0.0445

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000164

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000975

Gnomad4 OTH exome

AF:

0.00271

GnomAD4 genome

AF:

0.0119

AC:

1812

AN:

152162

Hom.:

Cov.:

AF XY:

0.0114

AC XY:

849

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.0412

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.0138

Alfa

AF:

0.00123

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.95

CADD

Benign

0.30

DANN

Benign

0.59

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