rs1145315

Variant names:

• chr18-54162585-C-T
• rs1145315
• NM_003927.5:c.1109+1938G>A

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+1938G>A 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 151,986 control chromosomes in the GnomAD database, including 12,837 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 (12837 hom., cov: 32)
• Consequence: MBD2 NM_003927.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.241
• Publications: 8 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 (EAS) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MBD2	NM_003927.5	c.1109+1938G>A		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+1938G>A		intron_variant	Intron 5 of 6	1	NM_003927.5	ENSP00000256429.3
MBD2	ENST00000578272.1	n.*336+1938G>A		intron_variant	Intron 5 of 5	5		ENSP00000462393.1

Frequencies

GnomAD3 genomes AF: 0.406 AC: 61617 AN: 151868 Hom.: 12813 Cov.: 32

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.453

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.569

Gnomad SAS AF: 0.511

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.475

Gnomad NFE AF: 0.360

Gnomad OTH AF: 0.395

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

GnomAD4 genome AF: 0.406 AC: 61695 AN: 151986 Hom.: 12837 Cov.: 32 AF XY: 0.415 AC XY: 30821 AN XY: 74310

African (AFR) AF: 0.418 AC: 17325 AN: 41446

American (AMR) AF: 0.453 AC: 6929 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1462 AN: 3466

East Asian (EAS) AF: 0.570 AC: 2941 AN: 5160

South Asian (SAS) AF: 0.511 AC: 2459 AN: 4812

European-Finnish (FIN) AF: 0.442 AC: 4668 AN: 10558

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.360 AC: 24486 AN: 67946

Other (OTH) AF: 0.400 AC: 844 AN: 2110

Alfa AF: 0.377 Hom.: 33771

Bravo AF: 0.404

Asia WGS AF: 0.539 AC: 1872 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	0.21
DANN	Benign	0.41
PhyloP100		-0.24
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: rs1145315; hg19: chr18-51688955; COSMIC: COSV56501735; COSMIC: COSV56501735;