rs10494303

Variant names:

• chr1-153920547-G-A
• rs10494303
• NM_020699.4:c.-2+2186C>T

Your query was ambiguous. Multiple possible variants found:

• chr1-153920547-G-A
• chr1-153920547-G-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.-2+2186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,050 control chromosomes in the GnomAD database, including 16,000 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 0.45 (16000 hom., cov: 32)
• Consequence: GATAD2B NM_020699.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10
• 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)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.754 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.-2+2186C>T		intron_variant	Intron 1 of 10	ENST00000368655.5	NP_065750.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.-2+2186C>T		intron_variant	Intron 1 of 10	1	NM_020699.4	ENSP00000357644.4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68654 AN: 151932 Hom.: 15978 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.496

Gnomad ASJ AF: 0.386

Gnomad EAS AF: 0.774

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.521

Gnomad MID AF: 0.494

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.458

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

GnomAD4 genome AF: 0.452 AC: 68716 AN: 152050 Hom.: 16000 Cov.: 32 AF XY: 0.459 AC XY: 34117 AN XY: 74332

African (AFR) AF: 0.428 AC: 17739 AN: 41442

American (AMR) AF: 0.496 AC: 7581 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 1339 AN: 3470

East Asian (EAS) AF: 0.774 AC: 4008 AN: 5176

South Asian (SAS) AF: 0.483 AC: 2330 AN: 4824

European-Finnish (FIN) AF: 0.521 AC: 5505 AN: 10576

Middle Eastern (MID) AF: 0.490 AC: 144 AN: 294

European-Non Finnish (NFE) AF: 0.423 AC: 28717 AN: 67968

Other (OTH) AF: 0.456 AC: 964 AN: 2114

Alfa AF: 0.436 Hom.: 52834

Bravo AF: 0.455

Asia WGS AF: 0.577 AC: 2010 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.4
DANN	Benign	0.53
PhyloP100		1.1
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: rs10494303; hg19: chr1-153893023;