rs145131801

chr1-153812083-G-A

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2 BP4_Strong BP6_Very_Strong BS2

The NM_020699.4(GATAD2B):c.1469C>T(p.Ala490Val) variant causes a missense change. The variant allele was found at a frequency of 0.00616 in 1,613,156 control chromosomes in the GnomAD database, including 38 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0043 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0063 (38 hom.)
• Consequence: GATAD2B NM_020699.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 4.97

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• PP2: Missense variant where missense usually causes diseases, GATAD2B
• BP4: Computational evidence support a benign effect (MetaRNN=0.0066090226).
• BP6: Variant 1-153812083-G-A is Benign according to our data. Variant chr1-153812083-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 211066.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd at 658 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATAD2B	NM_020699.4	c.1469C>T	p.Ala490Val	missense_variant	9/11	ENST00000368655.5
GATAD2B	XM_047426115.1	c.1472C>T	p.Ala491Val	missense_variant	9/11
GATAD2B	XM_047426117.1	c.1469C>T	p.Ala490Val	missense_variant	9/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATAD2B	ENST00000368655.5	c.1469C>T	p.Ala490Val	missense_variant	9/11	1	NM_020699.4	P1

Frequencies

GnomAD3 genomes AF: 0.00432 AC: 658 AN: 152166 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00334

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00264

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00754

Gnomad OTH AF: 0.00526

GnomAD3 exomes AF: 0.00464 AC: 1166 AN: 251342 Hom.: 6 AF XY: 0.00461 AC XY: 626 AN XY: 135850

Gnomad AFR exome AF: 0.00111

Gnomad AMR exome AF: 0.00252

Gnomad ASJ exome AF: 0.000595

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00431

Gnomad NFE exome AF: 0.00816

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00635 AC: 9275 AN: 1460872 Hom.: 38 Cov.: 30 AF XY: 0.00603 AC XY: 4386 AN XY: 726784

Gnomad4 AFR exome AF: 0.000986

Gnomad4 AMR exome AF: 0.00237

Gnomad4 ASJ exome AF: 0.000765

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000812

Gnomad4 FIN exome AF: 0.00498

Gnomad4 NFE exome AF: 0.00766

Gnomad4 OTH exome AF: 0.00489

GnomAD4 genome AF: 0.00432 AC: 658 AN: 152284 Hom.: 0 Cov.: 32 AF XY: 0.00398 AC XY: 296 AN XY: 74464

Gnomad4 AFR AF: 0.00116

Gnomad4 AMR AF: 0.00333

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00264

Gnomad4 NFE AF: 0.00754

Gnomad4 OTH AF: 0.00521

Alfa AF: 0.00659 Hom.: 3

Bravo AF: 0.00439

TwinsUK AF: 0.00809 AC: 30

ALSPAC AF: 0.00519 AC: 20

ESP6500AA AF: 0.00250 AC: 11

ESP6500EA AF: 0.00733 AC: 63

ExAC AF: 0.00521 AC: 632

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.00731

EpiControl AF: 0.00776

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:4

Benign, criteria provided, single submitter	clinical testing	Invitae	Feb 01, 2024	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Apr 01, 2024	GATAD2B: BS1, BS2 -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 05, 2018	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Jan 26, 2017	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

May 08, 2014

- -

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Apr 11, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.46	T
BayesDel_noAF	Benign	-0.42
Cadd	Uncertain	23
Dann	Uncertain	1.0
DEOGEN2	Benign	0.063	T;T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.0070	T
MetaRNN	Benign	0.0066	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;L;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.74	N;.;.
REVEL	Benign	0.077
Sift	Benign	0.13	T;.;.
Sift4G	Benign	0.27	T;T;T
Polyphen		0.60	P;P;.
Vest4		0.20
MVP		0.14
MPC		0.80
ClinPred		0.0062	T
GERP RS		5.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.69

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

Other links and lift over

dbSNP: rs145131801; hg19: chr1-153784559;