chr18-54174021-T-G

Variant names:

• chr18-54174021-T-G
• rs8094493
• NM_003927.5:c.841-7855A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0760
• Publications: 7 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=-0.87).
• 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 rank	MANE	Protein	UniProt
MBD2	NM_003927.5	c.841-7855A>C		intron_variant	Intron 3 of 6	ENST00000256429.8	NP_003918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD2	ENST00000256429.8	c.841-7855A>C		intron_variant	Intron 3 of 6	1	NM_003927.5	ENSP00000256429.3
MBD2	ENST00000578272.1	n.*68-7855A>C		intron_variant	Intron 3 of 5	5		ENSP00000462393.1

Frequencies

GnomAD3 genomes AF: 0.439 AC: 66594 AN: 151808 Hom.: 15180 Cov.: 32

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

African (AFR) AF: 0.541 AC: 22388 AN: 41412

American (AMR) AF: 0.348 AC: 5316 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.424 AC: 1470 AN: 3466

East Asian (EAS) AF: 0.426 AC: 2196 AN: 5156

South Asian (SAS) AF: 0.269 AC: 1296 AN: 4814

European-Finnish (FIN) AF: 0.350 AC: 3700 AN: 10574

Middle Eastern (MID) AF: 0.357 AC: 105 AN: 294

European-Non Finnish (NFE) AF: 0.426 AC: 28965 AN: 67914

Other (OTH) AF: 0.438 AC: 926 AN: 2116

Alfa AF: 0.391 Hom.: 6323

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
PhyloP100		-0.076
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: rs8094493; hg19: chr18-51700391;