rs886037647

Variant names:

• chr1-153818821-ACT-A
• rs886037647
• NM_020699.4:c.565_566delAG

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_566delAG​(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 rank	MANE	Protein	UniProt
GATAD2B	NM_020699.4	c.565_566delAG	p.Gln190AlafsTer34	frameshift_variant	Exon 4 of 11	ENST00000368655.5	NP_065750.1
GATAD2B	XM_047426115.1	c.568_569delAG	p.Gln191AlafsTer34	frameshift_variant	Exon 4 of 11		XP_047282071.1
GATAD2B	XM_047426117.1	c.565_566delAG	p.Gln190AlafsTer34	frameshift_variant	Exon 4 of 11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GATAD2B	ENST00000368655.5	c.565_566delAG	p.Gln190AlafsTer34	frameshift_variant	Exon 4 of 11	1	NM_020699.4	ENSP00000357644.4

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

Aug 10, 2019

GeneDx

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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) -

Jan 18, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

Aug 01, 2013

OMIM

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: literature only

- -

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;