NM_020699.4:c.-2+6389G>A

Variant names:

• chr1-153916344-C-T
• rs12033532
• NM_020699.4:c.-2+6389G>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+6389G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 151,144 control chromosomes in the GnomAD database, including 1,721 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 (1721 hom., cov: 31)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.621
• Publications: 0 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.473 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.-2+6389G>A		intron_variant	Intron 1 of 10	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.2+108G>A		intron_variant	Intron 1 of 10		XP_047282071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.-2+6389G>A		intron_variant	Intron 1 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19436 AN: 151086 Hom.: 1722 Cov.: 31

Gnomad AFR AF: 0.0736

Gnomad AMI AF: 0.219

Gnomad AMR AF: 0.0988

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.489

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.135

Gnomad NFE AF: 0.128

Gnomad OTH AF: 0.130

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

GnomAD4 genome AF: 0.129 AC: 19432 AN: 151144 Hom.: 1721 Cov.: 31 AF XY: 0.134 AC XY: 9879 AN XY: 73750

African (AFR) AF: 0.0736 AC: 3034 AN: 41226

American (AMR) AF: 0.0987 AC: 1496 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3470

East Asian (EAS) AF: 0.489 AC: 2517 AN: 5148

South Asian (SAS) AF: 0.156 AC: 750 AN: 4800

European-Finnish (FIN) AF: 0.207 AC: 2102 AN: 10178

Middle Eastern (MID) AF: 0.139 AC: 40 AN: 288

European-Non Finnish (NFE) AF: 0.128 AC: 8678 AN: 67866

Other (OTH) AF: 0.131 AC: 276 AN: 2100

Alfa AF: 0.128 Hom.: 1174

Bravo AF: 0.122

Asia WGS AF: 0.276 AC: 958 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.54
DANN	Benign	0.63
PhyloP100		-0.62
Mutation Taster		=98/2	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: rs12033532; hg19: chr1-153888820;