rs12043354

Variant names:

• chr1-153881948-C-T
• rs12043354
• NM_020699.4:c.-2+40785G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020699.4(GATAD2B):​c.-2+40785G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,914 control chromosomes in the GnomAD database, including 1,756 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1756 hom., cov: 32)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.111
• Publications: 1 publications found

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: ClinGen, G2P, Illumina, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.-2+40785G>A		intron_variant	Intron 1 of 10	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.2+34504G>A		intron_variant	Intron 1 of 10		XP_047282071.1
GATAD2B	XM_047426117.1	c.-2+16908G>A		intron_variant	Intron 1 of 10		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.-2+40785G>A		intron_variant	Intron 1 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19695 AN: 151796 Hom.: 1757 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.102

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.488

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.202

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.130

Gnomad OTH AF: 0.133

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19688 AN: 151914 Hom.: 1756 Cov.: 32 AF XY: 0.135 AC XY: 10017 AN XY: 74242

African (AFR) AF: 0.0731 AC: 3033 AN: 41470

American (AMR) AF: 0.102 AC: 1554 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 359 AN: 3468

East Asian (EAS) AF: 0.488 AC: 2510 AN: 5140

South Asian (SAS) AF: 0.151 AC: 724 AN: 4804

European-Finnish (FIN) AF: 0.202 AC: 2130 AN: 10536

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.130 AC: 8854 AN: 67954

Other (OTH) AF: 0.134 AC: 282 AN: 2106

Alfa AF: 0.122 Hom.: 234

Bravo AF: 0.123

Asia WGS AF: 0.263 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	7.6
DANN	Benign	0.73
PhyloP100		-0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs12043354; hg19: chr1-153854424;