18-54192756-G-C

Variant names:

• chr18-54192756-G-C
• rs609791
• NM_003927.5:c.703-3745C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003927.5(MBD2):​c.703-3745C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.841 in 152,162 control chromosomes in the GnomAD database, including 54,303 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 0.84 (54303 hom., cov: 31)
• Consequence: MBD2 NM_003927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82
• Publications: 2 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.974 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.703-3745C>G		intron	N/A	NP_003918.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MBD2	ENST00000256429.8	TSL:1 MANE Select	c.703-3745C>G		intron	N/A	ENSP00000256429.3
	MBD2	ENST00000578272.1	TSL:5	n.25-3745C>G		intron	N/A	ENSP00000462393.1

Frequencies

GnomAD3 genomes AF: 0.841 AC: 127835 AN: 152046 Hom.: 54243 Cov.: 31

Gnomad AFR AF: 0.955

Gnomad AMI AF: 0.810

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.834

Gnomad EAS AF: 0.997

Gnomad SAS AF: 0.778

Gnomad FIN AF: 0.821

Gnomad MID AF: 0.825

Gnomad NFE AF: 0.779

Gnomad OTH AF: 0.831

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

GnomAD4 genome AF: 0.841 AC: 127955 AN: 152162 Hom.: 54303 Cov.: 31 AF XY: 0.843 AC XY: 62717 AN XY: 74370

African (AFR) AF: 0.955 AC: 39659 AN: 41538

American (AMR) AF: 0.794 AC: 12131 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.834 AC: 2895 AN: 3470

East Asian (EAS) AF: 0.997 AC: 5161 AN: 5178

South Asian (SAS) AF: 0.778 AC: 3747 AN: 4816

European-Finnish (FIN) AF: 0.821 AC: 8688 AN: 10578

Middle Eastern (MID) AF: 0.832 AC: 243 AN: 292

European-Non Finnish (NFE) AF: 0.779 AC: 52928 AN: 67980

Other (OTH) AF: 0.834 AC: 1764 AN: 2114

Alfa AF: 0.715 Hom.: 2066

Bravo AF: 0.843

Asia WGS AF: 0.903 AC: 3142 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.025
DANN	Benign	0.37
PhyloP100		-1.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs609791; hg19: chr18-51719126;