Variant rs375391021 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2

The NM_020699.4(GATAD2B):c.1271G>T(p.Arg424Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,740 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R424H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

GATAD2B
NM_020699.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.07

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), GATAD2B. . Gene score misZ 3.161 (greater than the threshold 3.09). Trascript score misZ 3.9812 (greater than threshold 3.09). GenCC has associacion of gene with severe intellectual disability-poor language-strabismus-grimacing face-long fingers syndrome.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GATAD2B	NM_020699.4 linkuse as main transcript	c.1271G>T	p.Arg424Leu	missense_variant	8/11	ENST00000368655.5	NP_065750.1	Q8WXI9
GATAD2B	XM_047426115.1 linkuse as main transcript	c.1274G>T	p.Arg425Leu	missense_variant	8/11		XP_047282071.1
GATAD2B	XM_047426117.1 linkuse as main transcript	c.1271G>T	p.Arg424Leu	missense_variant	8/11		XP_047282073.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
GATAD2B	ENST00000368655.5 linkuse as main transcript	c.1271G>T	p.Arg424Leu	missense_variant	8/11	1	NM_020699.4	ENSP00000357644.4	Q8WXI9
GATAD2B	ENST00000634544.1 linkuse as main transcript	c.1271G>T	p.Arg424Leu	missense_variant	8/11	5		ENSP00000489184.1	Q8WXI9
GATAD2B	ENST00000634408.1 linkuse as main transcript	c.1223G>T	p.Arg408Leu	missense_variant	8/11	5		ENSP00000489595.1	A0A0U1RRM1
GATAD2B	ENST00000634564.1 linkuse as main transcript	c.524G>T	p.Arg175Leu	missense_variant	3/5	5		ENSP00000489309.1	A0A0U1RR30

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727170

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.33

BayesDel_addAF

Pathogenic

0.41

BayesDel_noAF

Pathogenic

0.35

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.74

D;D;.

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.96

.;.;D

M_CAP

Pathogenic

0.34

MetaRNN

Uncertain

0.74

D;D;D

MetaSVM

Pathogenic

1.0

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Pathogenic

0.89

PROVEAN

Uncertain

-4.2

D;.;.

REVEL

Pathogenic

0.76

Sift

Uncertain

0.0050

D;.;.

Sift4G

Uncertain

0.020

D;D;D

Polyphen

0.98

D;D;.

Vest4

0.64

MutPred

0.62

Gain of sheet (P = 0.0149);Gain of sheet (P = 0.0149);.;

MVP

0.84

MPC

2.0

ClinPred

0.94

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.47

gMVP

0.86

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over