rs114542403

Positions:

• chr1-153813440-G-C

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.1229C>G​(p.Ala410Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000292 in 1,613,526 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0016 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00015 (1 hom.)
• Consequence: GATAD2B NM_020699.4 missense
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.28

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=0.006309688).
• BP6: Variant 1-153813440-G-C is Benign according to our data. Variant chr1-153813440-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 211065.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 247 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GATAD2B	NM_020699.4	c.1229C>G	p.Ala410Gly	missense_variant	8/11	ENST00000368655.5
GATAD2B	XM_047426115.1	c.1232C>G	p.Ala411Gly	missense_variant	8/11
GATAD2B	XM_047426117.1	c.1229C>G	p.Ala410Gly	missense_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GATAD2B	ENST00000368655.5	c.1229C>G	p.Ala410Gly	missense_variant	8/11	1	NM_020699.4	P1
GATAD2B	ENST00000634544.1	c.1229C>G	p.Ala410Gly	missense_variant	8/11	5		P1
GATAD2B	ENST00000634408.1	c.1181C>G	p.Ala394Gly	missense_variant	8/11	5
GATAD2B	ENST00000634564.1	c.485C>G	p.Ala162Gly	missense_variant	3/5	5

Frequencies

GnomAD3 genomes AF: 0.00162 AC: 247 AN: 152110 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00582

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000328

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: 0.00

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.000370 AC: 93 AN: 251108 Hom.: 0 AF XY: 0.000273 AC XY: 37 AN XY: 135716

Gnomad AFR exome AF: 0.00523

Gnomad AMR exome AF: 0.000203

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000153 AC: 224 AN: 1461298 Hom.: 1 Cov.: 31 AF XY: 0.000127 AC XY: 92 AN XY: 726992

Gnomad4 AFR exome AF: 0.00571

Gnomad4 AMR exome AF: 0.000291

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.000282

GnomAD4 genome AF: 0.00162 AC: 247 AN: 152228 Hom.: 1 Cov.: 32 AF XY: 0.00152 AC XY: 113 AN XY: 74416

Gnomad4 AFR AF: 0.00580

Gnomad4 AMR AF: 0.000327

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000272 Hom.: 0

Bravo AF: 0.00185

ESP6500AA AF: 0.00477 AC: 21

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000379 AC: 46

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Invitae	Jan 24, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 24, 2020	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Dec 23, 2016

- -

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	0.072
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.065	T;T;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.0063	T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.075	N;N;.
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.7	N;.;.
REVEL	Benign	0.12
Sift	Benign	0.16	T;.;.
Sift4G	Benign	0.41	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.18
MVP		0.12
MPC		0.81
ClinPred		0.034	T
GERP RS		5.2
Varity_R		0.17
gMVP		0.26

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: rs114542403; hg19: chr1-153785916;