Genetic Variant GTF2IRD2:p.Val81Ile (chr7-74825050-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -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. 13/19 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

Publications

1 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173537.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF2IRD2	NM_173537.5	MANE Select	c.241G>A	p.Val81Ile	missense splice_region	Exon 4 of 16	NP_775808.4
GTF2IRD2	NM_001368300.2		c.727G>A	p.Val243Ile	missense splice_region	Exon 5 of 17	NP_001355229.1	A0A494C0I1
GTF2IRD2	NM_001388079.1		c.241G>A	p.Val81Ile	missense splice_region	Exon 4 of 16	NP_001375008.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GTF2IRD2	ENST00000451013.7	TSL:1 MANE Select	c.241G>A	p.Val81Ile	missense splice_region	Exon 4 of 16	ENSP00000406723.3	Q86UP8-1
ENSG00000289346	ENST00000625377.3	TSL:5	c.241G>A	p.Val81Ile	missense splice_region	Exon 11 of 23	ENSP00000486581.2
GTF2IRD2	ENST00000651129.1		c.727G>A	p.Val243Ile	missense splice_region	Exon 5 of 17	ENSP00000498563.1	A0A494C0I1

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

GnomAD2 exomes

AF:

0.0000895

AC:

AN:

111784

AF XY:

0.0000504

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000181

Gnomad OTH exome

AF:

0.000397

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

African (AFR)

AF:

0.000120

AC:

AN:

16618

American (AMR)

AF:

0.00

AC:

AN:

19260

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14428

East Asian (EAS)

AF:

0.000100

AC:

AN:

9964

South Asian (SAS)

AF:

0.00

AC:

AN:

59374

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2628

European-Non Finnish (NFE)

AF:

0.0000428

AC:

AN:

746832

Other (OTH)

AF:

0.000113

AC:

AN:

35408

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.441

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000230

AC:

AN:

87072

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

41302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

18716

American (AMR)

AF:

0.00

AC:

AN:

7602

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2470

East Asian (EAS)

AF:

0.00

AC:

AN:

2644

South Asian (SAS)

AF:

0.00

AC:

AN:

2308

European-Finnish (FIN)

AF:

0.00

AC:

AN:

5370

Middle Eastern (MID)

AF:

0.00

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.0000434

AC:

AN:

46058

Other (OTH)

AF:

0.00

AC:

AN:

1110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000745

Hom.:

ExAC

AF:

0.000110

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.071

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.76

CADD

Benign

0.11

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.011

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0036

LIST_S2

Benign

0.34

M_CAP

Benign

0.0011

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.14

PhyloP100

-0.91

PrimateAI

Uncertain

0.53

Sift4G

Benign

0.33

Polyphen

0.0

Vest4

0.050

MutPred

0.30

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

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over