18-54192756-G-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD2	NM_003927.5	c.703-3745C>G		intron_variant	Intron 2 of 6	ENST00000256429.8	NP_003918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD2	ENST00000256429.8	c.703-3745C>G		intron_variant	Intron 2 of 6	1	NM_003927.5	ENSP00000256429.3
MBD2	ENST00000578272.1	n.25-3745C>G		intron_variant	Intron 1 of 5	5		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

Gnomad4 AFR AF: 0.955

Gnomad4 AMR AF: 0.794

Gnomad4 ASJ AF: 0.834

Gnomad4 EAS AF: 0.997

Gnomad4 SAS AF: 0.778

Gnomad4 FIN AF: 0.821

Gnomad4 NFE AF: 0.779

Gnomad4 OTH AF: 0.834

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.025
DANN	Benign	0.37

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

Other links and lift over

dbSNP: rs609791; hg19: chr18-51719126;