Variant 2-148342533-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001378120.1(MBD5):c.-557+197A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 151,642 control chromosomes in the GnomAD database, including 5,366 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.25 ( 5366 hom., cov: 31)

Consequence

MBD5
NM_001378120.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.641

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 Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 2-148342533-A-T is Benign according to our data. Variant chr2-148342533-A-T is described in ClinVar as [Benign]. Clinvar id is 1243796.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD5	NM_001378120.1 linkuse as main transcript	c.-557+197A>T		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.-557+197A>T		intron_variant			NM_001378120.1	ENSP00000493871

Frequencies

GnomAD3 genomes

AF:

0.255

AC:

38604

AN:

151524

Hom.:

5351

Cov.:

show subpopulations

Gnomad AFR

AF:

0.137

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.333

Gnomad ASJ

AF:

0.184

Gnomad EAS

AF:

0.256

Gnomad SAS

AF:

0.336

Gnomad FIN

AF:

0.309

Gnomad MID

AF:

0.199

Gnomad NFE

AF:

0.298

Gnomad OTH

AF:

0.241

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

GnomAD4 genome

AF:

0.255

AC:

38658

AN:

151642

Hom.:

5366

Cov.:

AF XY:

0.258

AC XY:

19085

AN XY:

74092

show subpopulations

Gnomad4 AFR

AF:

0.137

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.184

Gnomad4 EAS

AF:

0.257

Gnomad4 SAS

AF:

0.337

Gnomad4 FIN

AF:

0.309

Gnomad4 NFE

AF:

0.298

Gnomad4 OTH

AF:

0.245

Alfa

AF:

0.292

Hom.:

873

Bravo

AF:

0.250

Asia WGS

AF:

0.332

AC:

1151

AN:

3470

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 23, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.20

DANN

Benign

0.39

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