18-54159155-T-C

Variant names:

• chr18-54159155-T-C
• rs4041245
• NM_003927.5:c.*12+610A>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.*12+610A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 151,952 control chromosomes in the GnomAD database, including 15,168 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 (15168 hom., cov: 31)
• Consequence: MBD2 NM_003927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0940
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.534 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD2	NM_003927.5	c.*12+610A>G		intron_variant	Intron 6 of 6	ENST00000256429.8	NP_003918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD2	ENST00000256429.8	c.*12+610A>G		intron_variant	Intron 6 of 6	1	NM_003927.5	ENSP00000256429.3
MBD2	ENST00000579025.1	n.183+610A>G		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes AF: 0.438 AC: 66549 AN: 151834 Hom.: 15159 Cov.: 31

Gnomad AFR AF: 0.540

Gnomad AMI AF: 0.298

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.424

Gnomad EAS AF: 0.427

Gnomad SAS AF: 0.268

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.426

Gnomad OTH AF: 0.439

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

GnomAD4 genome AF: 0.438 AC: 66590 AN: 151952 Hom.: 15168 Cov.: 31 AF XY: 0.430 AC XY: 31901 AN XY: 74266

African (AFR) AF: 0.540 AC: 22365 AN: 41432

American (AMR) AF: 0.347 AC: 5304 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1473 AN: 3470

East Asian (EAS) AF: 0.426 AC: 2197 AN: 5158

South Asian (SAS) AF: 0.268 AC: 1291 AN: 4820

European-Finnish (FIN) AF: 0.350 AC: 3694 AN: 10560

Middle Eastern (MID) AF: 0.354 AC: 104 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28969 AN: 67930

Other (OTH) AF: 0.437 AC: 922 AN: 2110

Alfa AF: 0.355 Hom.: 1871

Bravo AF: 0.445

Asia WGS AF: 0.365 AC: 1274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.73
PhyloP100		-0.094
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: rs4041245; hg19: chr18-51685525;