Variant chr2-148178611-A-C 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.-924-89A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 388,598 control chromosomes in the GnomAD database, including 25,987 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.31 ( 8363 hom., cov: 32)

Exomes 𝑓: 0.38 ( 17624 hom. )

Consequence

MBD5
NM_001378120.1 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0520

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=-0.83).

BP6

Variant 2-148178611-A-C is Benign according to our data. Variant chr2-148178611-A-C is described in ClinVar as [Benign]. Clinvar id is 1262738.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MBD5	NM_001378120.1 linkuse as main transcript	c.-924-89A>C		intron_variant		ENST00000642680.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MBD5	ENST00000642680.2 linkuse as main transcript	c.-924-89A>C		intron_variant			NM_001378120.1

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46862

AN:

152000

Hom.:

8368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.420

Gnomad AMR

AF:

0.341

Gnomad ASJ

AF:

0.429

Gnomad EAS

AF:

0.462

Gnomad SAS

AF:

0.300

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.462

Gnomad NFE

AF:

0.389

Gnomad OTH

AF:

0.335

GnomAD4 exome

AF:

0.381

AC:

90037

AN:

236480

Hom.:

17624

AF XY:

0.382

AC XY:

45877

AN XY:

120110

show subpopulations

Gnomad4 AFR exome

AF:

0.117

Gnomad4 AMR exome

AF:

0.361

Gnomad4 ASJ exome

AF:

0.441

Gnomad4 EAS exome

AF:

0.443

Gnomad4 SAS exome

AF:

0.302

Gnomad4 FIN exome

AF:

0.366

Gnomad4 NFE exome

AF:

0.385

Gnomad4 OTH exome

AF:

0.366

GnomAD4 genome

AF:

0.308

AC:

46866

AN:

152118

Hom.:

8363

Cov.:

AF XY:

0.307

AC XY:

22806

AN XY:

74360

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.341

Gnomad4 ASJ

AF:

0.429

Gnomad4 EAS

AF:

0.461

Gnomad4 SAS

AF:

0.301

Gnomad4 FIN

AF:

0.358

Gnomad4 NFE

AF:

0.389

Gnomad4 OTH

AF:

0.334

Alfa

AF:

0.342

Hom.:

1215

Bravo

AF:

0.304

Asia WGS

AF:

0.316

AC:

1095

AN:

3466

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

-0.83

CADD

Benign

3.3

DANN

Benign

0.76

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