Variant chr2-148178801-G-GT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6BS2

The NM_001378120.1(MBD5):c.-831+9dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000671 in 398,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00057 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00074 ( 0 hom. )

Consequence

MBD5
NM_001378120.1 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.617

Variant links:

Genes affected

MBD5 (HGNC:20444): (methyl-CpG binding domain protein 5) This gene encodes a member of the methyl-CpG-binding domain (MBD) family. The MBD consists of about 70 residues and is the minimal region required for a methyl-CpG-binding protein binding specifically to methylated DNA. In addition to the MBD domain, this protein contains a PWWP domain (Pro-Trp-Trp-Pro motif), which consists of 100-150 amino acids and is found in numerous proteins that are involved in cell division, growth and differentiation. Mutations in this gene cause an autosomal dominant type of cognitive disability. The encoded protein interacts with the polycomb repressive complex PR-DUB which catalyzes the deubiquitination of a lysine residue of histone 2A. Haploinsufficiency of this gene is associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures. Alternatively spliced transcript variants have been found, but their full-length nature is not determined. [provided by RefSeq, Jul 2017]

MBD5 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP6

Variant 2-148178801-G-GT is Benign according to our data. Variant chr2-148178801-G-GT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 206049.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.

BS2

High AC in GnomAd4 at 86 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD5	NM_001378120.1 linkuse as main transcript	c.-831+9dup		intron_variant		ENST00000642680.2	NP_001365049.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD5	ENST00000642680.2 linkuse as main transcript	c.-831+9dup		intron_variant			NM_001378120.1	ENSP00000493871

Frequencies

GnomAD3 genomes

AF:

0.000565

AC:

AN:

152138

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000328

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000736

AC:

181

AN:

246044

Hom.:

Cov.:

AF XY:

0.000762

AC XY:

AN XY:

124750

show subpopulations

Gnomad4 AFR exome

AF:

0.000140

Gnomad4 AMR exome

AF:

0.000135

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000471

Gnomad4 NFE exome

AF:

0.00103

Gnomad4 OTH exome

AF:

0.000428

GnomAD4 genome

AF:

0.000565

AC:

AN:

152138

Hom.:

Cov.:

AF XY:

0.000444

AC XY:

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.0000966

Gnomad4 AMR

AF:

0.000328

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.000423

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Intellectual Disability, Dominant

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 24, 2014

The variant is found in INFANT-EPI,EPILEPSY panel(s). -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

MBD5: BS1 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over