chr1-153806760-C-A

Variant names:

• chr1-153806760-C-A
• rs1127092
• NM_020699.4:c.*3417G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_020699.4(GATAD2B):​c.*3417G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000767 in 130,316 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000077 (0 hom., cov: 26)
• Consequence: GATAD2B NM_020699.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0690
• Publications: 7 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.*3417G>T		3_prime_UTR_variant	Exon 11 of 11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.*3417G>T		3_prime_UTR_variant	Exon 11 of 11		XP_047282071.1
GATAD2B	XM_047426117.1	c.*3417G>T		3_prime_UTR_variant	Exon 11 of 11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.*3417G>T		3_prime_UTR_variant	Exon 11 of 11	1	NM_020699.4	ENSP00000357644.4
GATAD2B	ENST00000637918.1	c.133+4971G>T		intron_variant	Intron 2 of 3	5		ENSP00000490724.1
ENSG00000291199	ENST00000820544.1	n.296+12555C>A		intron_variant	Intron 1 of 1

Frequencies

GnomAD3 genomes AF: 0.00000767 AC: 1 AN: 130316 Hom.: 0 Cov.: 26

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000243

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.00000767 AC: 1 AN: 130316 Hom.: 0 Cov.: 26 AF XY: 0.0000160 AC XY: 1 AN XY: 62392

African (AFR) AF: 0.00 AC: 0 AN: 33676

American (AMR) AF: 0.00 AC: 0 AN: 11854

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3118

East Asian (EAS) AF: 0.00 AC: 0 AN: 4928

South Asian (SAS) AF: 0.000243 AC: 1 AN: 4108

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8310

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 288

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61452

Other (OTH) AF: 0.00 AC: 0 AN: 1750

Alfa AF: 0.00 Hom.: 157

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.89
DANN	Benign	0.67
PhyloP100		-0.069
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1127092; hg19: chr1-153779236;