18-54154387-T-C

Position:

• chr18-54154387-T-C

Variant summary

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

The NM_003927.5(MBD2):​c.*937A>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 0.743 in 152,030 control chromosomes in the GnomAD database, including 42,754 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 0.74 (42754 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: MBD2 NM_003927.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0900

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MBD2	NM_003927.5	c.*937A>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	c.*937A>G		3_prime_UTR_variant	7/7	1	NM_003927.5	ENSP00000256429.3

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112887 AN: 151908 Hom.: 42706 Cov.: 31

Gnomad AFR AF: 0.862

Gnomad AMI AF: 0.764

Gnomad AMR AF: 0.727

Gnomad ASJ AF: 0.781

Gnomad EAS AF: 0.969

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.718

Gnomad NFE AF: 0.663

Gnomad OTH AF: 0.737

GnomAD4 exome AF: 0.500 AC: 2 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 2 AN XY: 4

Gnomad4 ASJ exome AF: 0.500

Gnomad4 NFE exome AF: 0.500

GnomAD4 genome AF: 0.743 AC: 112994 AN: 152026 Hom.: 42754 Cov.: 31 AF XY: 0.747 AC XY: 55509 AN XY: 74298

Gnomad4 AFR AF: 0.862

Gnomad4 AMR AF: 0.726

Gnomad4 ASJ AF: 0.781

Gnomad4 EAS AF: 0.969

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.700

Gnomad4 NFE AF: 0.663

Gnomad4 OTH AF: 0.741

Alfa AF: 0.694 Hom.: 13436

Bravo AF: 0.748

Asia WGS AF: 0.848 AC: 2952 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.75

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: rs1259938; hg19: chr18-51680757;