Genetic Variant NM_020699.4:c.1765A>G (chr1-153810194-T-C) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_020699.4(GATAD2B):c.1765A>G(p.Ile589Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,458,648 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. I589I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

GATAD2B
NM_020699.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.40

Publications

0 publications found

Variant links:

Genes affected

GATAD2B (HGNC:30778): (GATA zinc finger domain containing 2B) This gene encodes a zinc finger protein transcriptional repressor. The encoded protein is part of the methyl-CpG-binding protein-1 complex, which represses gene expression by deacetylating methylated nucleosomes. Mutations in this gene are linked to intellectual disability and dysmorphic features associated with cognitive disability. [provided by RefSeq, Jun 2016]

GATAD2B Gene-Disease associations (from GenCC):

severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, ClinGen, Orphanet, Labcorp Genetics (formerly Invitae), Illumina

GATAD2B links:

ENSG00000291199 (HGNC:):

ENSG00000291199 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.13863).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD2B	NM_020699.4	MANE Select	c.1765A>G	p.Ile589Val	missense	Exon 11 of 11	NP_065750.1	Q8WXI9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.1765A>G	p.Ile589Val	missense	Exon 11 of 11	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000634544.1	TSL:5	c.1765A>G	p.Ile589Val	missense	Exon 11 of 11	ENSP00000489184.1	Q8WXI9
GATAD2B	ENST00000867096.1		c.1765A>G	p.Ile589Val	missense	Exon 12 of 12	ENSP00000537155.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000806

AC:

AN:

248272

AF XY:

0.00000744

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000298

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1458648

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725500

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33286

American (AMR)

AF:

0.0000682

AC:

AN:

44006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26072

East Asian (EAS)

AF:

0.00

AC:

AN:

39524

South Asian (SAS)

AF:

0.00

AC:

AN:

85706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53406

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5756

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1110628

Other (OTH)

AF:

0.0000166

AC:

AN:

60264

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.467

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.047

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.0065

MetaRNN

Benign

0.14

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

1.4

PrimateAI

Uncertain

0.69

PROVEAN

Benign

0.50

REVEL

Benign

0.13

Sift

Benign

0.52

Sift4G

Benign

1.0

Polyphen

0.82

Vest4

0.29

MutPred

0.057

Gain of MoRF binding (P = 0.1234)

MVP

0.22

MPC

1.2

ClinPred

0.22

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.046

gMVP

0.55

Mutation Taster

=89/11

polymorphism

(source)

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

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over