rs9427232

Variant names:

• chr1-153820482-G-A
• rs9427232
• NM_020699.4:c.336-747C>T

Variant summary

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

The NM_020699.4(GATAD2B):​c.336-747C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 152,000 control chromosomes in the GnomAD database, including 13,889 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 0.41 (13889 hom., cov: 31)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.514
• Publications: 10 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)

ENSG00000291199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.512 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.336-747C>T		intron_variant	Intron 2 of 10	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.339-747C>T		intron_variant	Intron 2 of 10		XP_047282071.1
GATAD2B	XM_047426117.1	c.336-747C>T		intron_variant	Intron 2 of 10		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.336-747C>T		intron_variant	Intron 2 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62286 AN: 151880 Hom.: 13885 Cov.: 31

Gnomad AFR AF: 0.289

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.340

Gnomad FIN AF: 0.432

Gnomad MID AF: 0.437

Gnomad NFE AF: 0.517

Gnomad OTH AF: 0.433

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

GnomAD4 genome AF: 0.410 AC: 62303 AN: 152000 Hom.: 13889 Cov.: 31 AF XY: 0.401 AC XY: 29777 AN XY: 74314

African (AFR) AF: 0.288 AC: 11958 AN: 41456

American (AMR) AF: 0.345 AC: 5257 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1973 AN: 3470

East Asian (EAS) AF: 0.0586 AC: 304 AN: 5184

South Asian (SAS) AF: 0.341 AC: 1645 AN: 4830

European-Finnish (FIN) AF: 0.432 AC: 4550 AN: 10528

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.517 AC: 35116 AN: 67956

Other (OTH) AF: 0.436 AC: 922 AN: 2114

Alfa AF: 0.449 Hom.: 2798

Bravo AF: 0.393

Asia WGS AF: 0.235 AC: 816 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.4
DANN	Benign	0.72
PhyloP100		-0.51
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: rs9427232; hg19: chr1-153792958;