Genetic Variant GTF2IRD2:p.Glu31Lys (chr7-74836288-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_173537.5(GTF2IRD2):c.91G>A(p.Glu31Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000013 in 1,609,616 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

GTF2IRD2
NM_173537.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.29

Variant links:

Genes affected

GTF2IRD2 (HGNC:30775): (GTF2I repeat domain containing 2) This gene is one of several closely related genes on chromosome 7 encoding proteins containing helix-loop-helix motifs. These proteins may function as regulators of transcription. The encoded protein is unique in that its C-terminus is derived from CHARLIE8 transposable element sequence. This gene is located in a region of chromosome 7 that is deleted in Williams-Beuren syndrome, and loss of this locus may contribute to the cognitive phenotypes observed in this disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

GTF2IRD2 links:

ENSG00000289346 (HGNC:):

ENSG00000289346 links:

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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=0.009238124).

BP6

Variant 7-74836288-C-T is Benign according to our data. Variant chr7-74836288-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657605.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2IRD2	NM_173537.5 link	c.91G>A	p.Glu31Lys	missense_variant	Exon 2 of 16	ENST00000451013.7	NP_775808.4	Q86UP8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GTF2IRD2	ENST00000451013.7 link	c.91G>A	p.Glu31Lys	missense_variant	Exon 2 of 16	1	NM_173537.5	ENSP00000406723.3		Q86UP8-1
ENSG00000289346	ENST00000625377.3 link	c.91G>A	p.Glu31Lys	missense_variant	Exon 9 of 23	5		ENSP00000486581.2		A0A0D9SF80

Frequencies

GnomAD3 genomes

AF:

0.00000673

AC:

AN:

148640

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00205

AC:

129

AN:

63024

Hom.:

AF XY:

0.00176

AC XY:

AN XY:

31786

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:

0.000244

Gnomad FIN exome

AF:

0.0197

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000137

AC:

AN:

1460976

Hom.:

Cov.:

AF XY:

0.0000165

AC XY:

AN XY:

726874

show subpopulations

Gnomad4 AFR exome

AF:

0.000182

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000540

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.00000673

AC:

AN:

148640

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

72666

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.000694

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GTF2IRD2: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.024

T;.;.

Eigen

Uncertain

0.21

Eigen_PC

Benign

0.021

FATHMM_MKL

Benign

0.74

LIST_S2

Uncertain

0.97

D;D;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.0092

T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.5

M;.;M

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

-0.87

N;.;.

Sift

Benign

0.25

T;.;.

Sift4G

Uncertain

0.0080

D;D;D

Polyphen

1.0

D;.;D

Vest4

0.33

MVP

0.040

ClinPred

0.24

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.34

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