18-54174021-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003927.5(MBD2):​c.841-7855A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 151,926 control chromosomes in the GnomAD database, including 15,189 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 0.44 ( 15189 hom., cov: 32)

Consequence

MBD2
NM_003927.5 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0760
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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MBD2NM_003927.5 linkuse as main transcriptc.841-7855A>C intron_variant ENST00000256429.8 NP_003918.1 Q9UBB5-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MBD2ENST00000256429.8 linkuse as main transcriptc.841-7855A>C intron_variant 1 NM_003927.5 ENSP00000256429.3 Q9UBB5-1
MBD2ENST00000578272.1 linkuse as main transcriptn.*68-7855A>C intron_variant 5 ENSP00000462393.1 J3KSA7

Frequencies

GnomAD3 genomes
AF:
0.439
AC:
66594
AN:
151808
Hom.:
15180
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.541
Gnomad AMI
AF:
0.300
Gnomad AMR
AF:
0.349
Gnomad ASJ
AF:
0.424
Gnomad EAS
AF:
0.427
Gnomad SAS
AF:
0.269
Gnomad FIN
AF:
0.350
Gnomad MID
AF:
0.348
Gnomad NFE
AF:
0.427
Gnomad OTH
AF:
0.439
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.439
AC:
66634
AN:
151926
Hom.:
15189
Cov.:
32
AF XY:
0.430
AC XY:
31938
AN XY:
74268
show subpopulations
Gnomad4 AFR
AF:
0.541
Gnomad4 AMR
AF:
0.348
Gnomad4 ASJ
AF:
0.424
Gnomad4 EAS
AF:
0.426
Gnomad4 SAS
AF:
0.269
Gnomad4 FIN
AF:
0.350
Gnomad4 NFE
AF:
0.426
Gnomad4 OTH
AF:
0.438
Alfa
AF:
0.385
Hom.:
5478
Bravo
AF:
0.445
Asia WGS
AF:
0.365
AC:
1273
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.87
CADD
Benign
2.0
DANN
Benign
0.54

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.

Other links and lift over

dbSNP: rs8094493; hg19: chr18-51700391; API