7-74825050-C-T

Variant names:

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_173537.5(GTF2IRD2):c.241G>A(p.Val81Ile) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000023 ( 0 hom., cov: 12)

Exomes 𝑓: 0.000041 ( 2 hom. )

Failed GnomAD Quality Control

Consequence

GTF2IRD2
NM_173537.5 missense, splice_region

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.914

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.044751585).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GTF2IRD2	NM_173537.5 link	c.241G>A	p.Val81Ile	missense_variant, splice_region_variant	Exon 4 of 16	ENST00000451013.7	NP_775808.4	Q86UP8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GTF2IRD2	ENST00000451013.7 link	c.241G>A	p.Val81Ile	missense_variant, splice_region_variant	Exon 4 of 16	1	NM_173537.5	ENSP00000406723.3	Q86UP8-1
ENSG00000289346	ENST00000625377.3 link	c.241G>A	p.Val81Ile	missense_variant, splice_region_variant	Exon 11 of 23	5		ENSP00000486581.2	A0A0D9SF80
GTF2IRD2	ENST00000651129.1 link	c.727G>A	p.Val243Ile	missense_variant, splice_region_variant	Exon 5 of 17			ENSP00000498563.1	A0A494C0I1
GTF2IRD2	ENST00000619775.1 link	n.416G>A		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 5	2

Frequencies

GnomAD3 genomes

AF:

0.0000230

AC:

AN:

87072

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:

0.0000434

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000414

AC:

AN:

941690

Hom.:

Cov.:

AF XY:

0.0000383

AC XY:

AN XY:

470124

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000100

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000428

Gnomad4 OTH exome

AF:

0.000113

GnomAD4 genome

AF:

0.0000230

AC:

AN:

87072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

41302

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:

0.0000434

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000745

Hom.:

ExAC

AF:

0.000110

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.241G>A (p.V81I) alteration is located in exon 4 (coding exon 3) of the GTF2IRD2 gene. This alteration results from a G to A substitution at nucleotide position 241, causing the valine (V) at amino acid position 81 to be replaced by an isoleucine (I). 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

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.11

DANN

Benign

0.92

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.34

T;T

M_CAP

Benign

0.0011

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

N;.

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.33

T;T

Polyphen

0.0

B;.

Vest4

0.050

MutPred

0.30

Gain of methylation at K78 (P = 0.1138);Gain of methylation at K78 (P = 0.1138);

MVP

0.014

ClinPred

0.025

GERP RS

-5.4

Varity_R

0.011

gMVP

0.014

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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