Genetic Variant MBD2:c.*450A>G (chr18-54154874-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003927.5(MBD2):c.*450A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,504 control chromosomes in the GnomAD database, including 10,751 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.37 ( 10716 hom., cov: 32)

Exomes 𝑓: 0.37 ( 35 hom. )

Consequence

MBD2
NM_003927.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.10

Publications

18 publications found

Variant links:

Genes affected

MBD2 (HGNC:6917): (methyl-CpG binding domain protein 2) DNA methylation is the major modification of eukaryotic genomes and plays an essential role in mammalian development. Human proteins MECP2, MBD1, MBD2, MBD3, and MBD4 comprise a family of nuclear proteins related by the presence in each of a methyl-CpG binding domain (MBD). Each of these proteins, with the exception of MBD3, is capable of binding specifically to methylated DNA. MECP2, MBD1 and MBD2 can also repress transcription from methylated gene promoters. The protein encoded by this gene may function as a mediator of the biological consequences of the methylation signal. It is also reported that the this protein functions as a demethylase to activate transcription, as DNA methylation causes gene silencing. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Feb 2011]

MBD2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003927.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD2	NM_003927.5	MANE Select	c.*450A>G		3_prime_UTR	Exon 7 of 7	NP_003918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD2	ENST00000256429.8	TSL:1 MANE Select	c.*450A>G		3_prime_UTR	Exon 7 of 7	ENSP00000256429.3

Frequencies

GnomAD3 genomes

AF:

0.366

AC:

55579

AN:

151952

Hom.:

10714

Cov.:

show subpopulations

Gnomad AFR

AF:

0.271

Gnomad AMI

AF:

0.299

Gnomad AMR

AF:

0.316

Gnomad ASJ

AF:

0.439

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.305

Gnomad FIN

AF:

0.366

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.428

Gnomad OTH

AF:

0.390

GnomAD4 exome

AF:

0.373

AC:

162

AN:

434

Hom.:

Cov.:

AF XY:

0.364

AC XY:

AN XY:

264

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.376

AC:

160

AN:

426

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.250

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.453

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.366

AC:

55603

AN:

152070

Hom.:

10716

Cov.:

AF XY:

0.361

AC XY:

26803

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.271

AC:

11250

AN:

41484

American (AMR)

AF:

0.316

AC:

4822

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.439

AC:

1521

AN:

3464

East Asian (EAS)

AF:

0.458

AC:

2375

AN:

5182

South Asian (SAS)

AF:

0.305

AC:

1467

AN:

4814

European-Finnish (FIN)

AF:

0.366

AC:

3867

AN:

10570

Middle Eastern (MID)

AF:

0.357

AC:

105

AN:

294

European-Non Finnish (NFE)

AF:

0.428

AC:

29101

AN:

67974

Other (OTH)

AF:

0.389

AC:

822

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1779

3558

5336

7115

8894

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

538

1076

1614

2152

2690

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.408

Hom.:

41700

Bravo

AF:

0.360

Asia WGS

AF:

0.386

AC:

1345

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

(source)

DANN

Benign

0.74

PhyloP100

3.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over