1-153818821-ACT-A

Position:

• chr1-153818821-ACT-A

Variant summary

Our verdict is Pathogenic. Variant got 18 ACMG points: 18P and 0B. PVS1 PM2 PP5_Very_Strong

The NM_020699.4(GATAD2B):​c.565_566del​(p.Gln190AlafsTer34) variant causes a frameshift change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (★★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: GATAD2B NM_020699.4 frameshift
• Clinical Significance: Pathogenic criteria provided, multiple submitters, no conflicts P:3
• Conservation: PhyloP100: 6.15

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]

ACMG classification

Verdict is Pathogenic. Variant got 18 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 1-153818821-ACT-A is Pathogenic according to our data. Variant chr1-153818821-ACT-A is described in ClinVar as [Pathogenic]. Clinvar id is 65423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.565_566del	p.Gln190AlafsTer34	frameshift_variant	4/11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.568_569del	p.Gln191AlafsTer34	frameshift_variant	4/11		XP_047282071.1
GATAD2B	XM_047426117.1	c.565_566del	p.Gln190AlafsTer34	frameshift_variant	4/11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.565_566del	p.Gln190AlafsTer34	frameshift_variant	4/11	1	NM_020699.4	ENSP00000357644	P1

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Pathogenic:2

Pathogenic, criteria provided, single submitter	clinical testing	GeneDx	Aug 10, 2019	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 31949314, 23644463) -
Pathogenic, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2023	For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of GATAD2B-related conditions (PMID: 23644463). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln190Alafs*34) in the GATAD2B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in GATAD2B are known to be pathogenic (PMID: 23033978, 25356899, 27159321). -

Severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome Pathogenic:1

Pathogenic, no assertion criteria provided

literature only

OMIM

Aug 01, 2013

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs886037647; hg19: chr1-153791297;