2-148178801-G-GT
Variant names:
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2
The NM_001378120.1(MBD5):c.-831+9dupT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000671 in 398,182 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Genomes: 𝑓 0.00057 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00074 ( 0 hom. )
Consequence
MBD5
NM_001378120.1 intron
NM_001378120.1 intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.617
Genes affected
MBD5 (HGNC:20444): (methyl-CpG binding domain protein 5) This gene encodes a member of the methyl-CpG-binding domain (MBD) family. The MBD consists of about 70 residues and is the minimal region required for a methyl-CpG-binding protein binding specifically to methylated DNA. In addition to the MBD domain, this protein contains a PWWP domain (Pro-Trp-Trp-Pro motif), which consists of 100-150 amino acids and is found in numerous proteins that are involved in cell division, growth and differentiation. Mutations in this gene cause an autosomal dominant type of cognitive disability. The encoded protein interacts with the polycomb repressive complex PR-DUB which catalyzes the deubiquitination of a lysine residue of histone 2A. Haploinsufficiency of this gene is associated with a syndrome involving microcephaly, intellectual disabilities, severe speech impairment, and seizures. Alternatively spliced transcript variants have been found, but their full-length nature is not determined. [provided by RefSeq, Jul 2017]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -9 ACMG points.
BP6
Variant 2-148178801-G-GT is Benign according to our data. Variant chr2-148178801-G-GT is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 206049.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Benign=1, Uncertain_significance=1}.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000565 (86/152138) while in subpopulation NFE AF= 0.0011 (75/68022). AF 95% confidence interval is 0.000902. There are 0 homozygotes in gnomad4. There are 33 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck.
BS2
High AC in GnomAd4 at 86 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MBD5 | NM_001378120.1 | c.-831+9dupT | intron_variant | Intron 2 of 13 | ENST00000642680.2 | NP_001365049.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MBD5 | ENST00000642680.2 | c.-831+8_-831+9insT | intron_variant | Intron 2 of 13 | NM_001378120.1 | ENSP00000493871.2 |
Frequencies
GnomAD3 genomes AF: 0.000565 AC: 86AN: 152138Hom.: 0 Cov.: 31
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GnomAD4 exome AF: 0.000736 AC: 181AN: 246044Hom.: 0 Cov.: 0 AF XY: 0.000762 AC XY: 95AN XY: 124750
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GnomAD4 genome AF: 0.000565 AC: 86AN: 152138Hom.: 0 Cov.: 31 AF XY: 0.000444 AC XY: 33AN XY: 74326
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ClinVar
Significance: Conflicting classifications of pathogenicity
Submissions summary: Uncertain:1Benign:2
Revision: criteria provided, conflicting classifications
LINK: link
Submissions by phenotype
Intellectual Disability, Dominant Uncertain:1
Jun 14, 2016
Illumina Laboratory Services, Illumina
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing
- -
not specified Benign:1
Mar 24, 2014
GeneDx
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
The variant is found in INFANT-EPI,EPILEPSY panel(s). -
not provided Benign:1
Dec 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing
MBD5: BS1 -
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at