chr18-54154874-T-C

Position:

• chr18-54154874-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000256429.8(MBD2):​c.*450A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.366 in 152,504 control chromosomes in the GnomAD database, including 10,751 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 0.37 (10716 hom., cov: 32)
  • Exomes 𝑓: 0.37 (35 hom.)
• Consequence: MBD2 ENST00000256429.8 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.10

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=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD2	NM_003927.5	c.*450A>G		3_prime_UTR_variant	7/7	ENST00000256429.8	NP_003918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MBD2	ENST00000256429.8	c.*450A>G		3_prime_UTR_variant	7/7	1	NM_003927.5	ENSP00000256429	P1

Frequencies

GnomAD3 genomes AF: 0.366 AC: 55579 AN: 151952 Hom.: 10714 Cov.: 32

Gnomad AFR AF: 0.271

Gnomad AMI AF: 0.299

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.439

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.428

Gnomad OTH AF: 0.390

GnomAD4 exome AF: 0.373 AC: 162 AN: 434 Hom.: 35 Cov.: 0 AF XY: 0.364 AC XY: 96 AN XY: 264

Gnomad4 FIN exome AF: 0.376

Gnomad4 NFE exome AF: 0.250

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.366 AC: 55603 AN: 152070 Hom.: 10716 Cov.: 32 AF XY: 0.361 AC XY: 26803 AN XY: 74328

Gnomad4 AFR AF: 0.271

Gnomad4 AMR AF: 0.316

Gnomad4 ASJ AF: 0.439

Gnomad4 EAS AF: 0.458

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.428

Gnomad4 OTH AF: 0.389

Alfa AF: 0.424 Hom.: 27458

Bravo AF: 0.360

Asia WGS AF: 0.386 AC: 1345 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Benign	0.74
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs7614; hg19: chr18-51681244; COSMIC: COSV56503137; COSMIC: COSV56503137;