18-54163522-A-G

Variant names:

• chr18-54163522-A-G
• rs1145317
• NM_003927.5:c.1109+1001T>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.1109+1001T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.406 in 151,860 control chromosomes in the GnomAD database, including 12,826 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 0.41 (12826 hom., cov: 31)
• Consequence: MBD2 NM_003927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690
• Publications: 1 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.551 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD2	NM_003927.5	c.1109+1001T>C		intron_variant	Intron 5 of 6	ENST00000256429.8	NP_003918.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MBD2	ENST00000256429.8	c.1109+1001T>C		intron_variant	Intron 5 of 6	1	NM_003927.5	ENSP00000256429.3
MBD2	ENST00000578272.1	n.*336+1001T>C		intron_variant	Intron 5 of 5	5		ENSP00000462393.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61636 AN: 151742 Hom.: 12802 Cov.: 31

Gnomad AFR AF: 0.412

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.454

Gnomad ASJ AF: 0.421

Gnomad EAS AF: 0.567

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.394

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

GnomAD4 genome AF: 0.406 AC: 61712 AN: 151860 Hom.: 12826 Cov.: 31 AF XY: 0.415 AC XY: 30804 AN XY: 74198

African (AFR) AF: 0.413 AC: 17079 AN: 41396

American (AMR) AF: 0.454 AC: 6930 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.421 AC: 1457 AN: 3460

East Asian (EAS) AF: 0.569 AC: 2918 AN: 5132

South Asian (SAS) AF: 0.511 AC: 2452 AN: 4800

European-Finnish (FIN) AF: 0.443 AC: 4669 AN: 10536

Middle Eastern (MID) AF: 0.473 AC: 138 AN: 292

European-Non Finnish (NFE) AF: 0.365 AC: 24785 AN: 67966

Other (OTH) AF: 0.400 AC: 840 AN: 2102

Alfa AF: 0.393 Hom.: 3500

Bravo AF: 0.404

Asia WGS AF: 0.539 AC: 1873 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	6.4
DANN	Benign	0.57
PhyloP100		0.069
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: rs1145317; hg19: chr18-51689892;