1-153822520-G-C

Variant names:

• chr1-153822520-G-C
• rs6427298
• NM_020699.4:c.336-2785C>G

Variant summary

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

The NM_020699.4(GATAD2B):​c.336-2785C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.842 in 152,088 control chromosomes in the GnomAD database, including 54,293 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 0.84 (54293 hom., cov: 32)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.58
• 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)

ENSG00000291199 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.884 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020699.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD2B	NM_020699.4	MANE Select	c.336-2785C>G		intron	N/A	NP_065750.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GATAD2B	ENST00000368655.5	TSL:1 MANE Select	c.336-2785C>G		intron	N/A	ENSP00000357644.4
	GATAD2B	ENST00000634544.1	TSL:5	c.336-2785C>G		intron	N/A	ENSP00000489184.1
	GATAD2B	ENST00000634408.1	TSL:5	c.336-2785C>G		intron	N/A	ENSP00000489595.1

Frequencies

GnomAD3 genomes AF: 0.842 AC: 127903 AN: 151970 Hom.: 54234 Cov.: 32

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.785

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.910

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.847

Gnomad FIN AF: 0.798

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.855

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

GnomAD4 genome AF: 0.842 AC: 128023 AN: 152088 Hom.: 54293 Cov.: 32 AF XY: 0.838 AC XY: 62299 AN XY: 74350

African (AFR) AF: 0.811 AC: 33655 AN: 41500

American (AMR) AF: 0.897 AC: 13694 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.910 AC: 3156 AN: 3468

East Asian (EAS) AF: 0.512 AC: 2628 AN: 5130

South Asian (SAS) AF: 0.849 AC: 4084 AN: 4812

European-Finnish (FIN) AF: 0.798 AC: 8442 AN: 10580

Middle Eastern (MID) AF: 0.847 AC: 249 AN: 294

European-Non Finnish (NFE) AF: 0.876 AC: 59598 AN: 68010

Other (OTH) AF: 0.854 AC: 1804 AN: 2112

Alfa AF: 0.850 Hom.: 2739

Bravo AF: 0.844

Asia WGS AF: 0.728 AC: 2533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.11
DANN	Benign	0.42
PhyloP100		-4.6
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: rs6427298; hg19: chr1-153794996;