NM_001378778.1:c.2155-25A>T
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2
The NM_001378778.1(MPDZ):c.2155-25A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000188 in 1,593,622 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
MPDZ
NM_001378778.1 intron
NM_001378778.1 intron
Scores
2
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 0.213
Publications
3 publications found
Genes affected
MPDZ (HGNC:7208): (multiple PDZ domain crumbs cell polarity complex component) The protein encoded by this gene has multiple PDZ domains, which are hallmarks of protein-protein interactions. The encoded protein is known to interact with the HTR2C receptor and may cause it to clump at the cell surface. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]
MPDZ Gene-Disease associations (from GenCC):
- hydrocephalus, nonsyndromic, autosomal recessive 2Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Genomics England PanelApp, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Laboratory for Molecular Medicine
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001378778.1. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MPDZ | NM_001378778.1 | MANE Select | c.2155-25A>T | intron | N/A | NP_001365707.1 | |||
| MPDZ | NM_001375413.1 | c.2155-25A>T | intron | N/A | NP_001362342.1 | ||||
| MPDZ | NM_001330637.2 | c.2155-25A>T | intron | N/A | NP_001317566.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| MPDZ | ENST00000319217.12 | TSL:5 MANE Select | c.2155-25A>T | intron | N/A | ENSP00000320006.7 | |||
| MPDZ | ENST00000541718.5 | TSL:1 | c.2155-25A>T | intron | N/A | ENSP00000439807.1 | |||
| MPDZ | ENST00000447879.6 | TSL:1 | c.2155-25A>T | intron | N/A | ENSP00000415208.1 |
Frequencies
GnomAD3 genomes 0.00000658 AC: 1AN: 152022Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152022
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD2 exomes AF: 0.00000420 AC: 1AN: 237858 AF XY: 0.00 show subpopulations
GnomAD2 exomes
AF:
AC:
1
AN:
237858
AF XY:
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000139 AC: 2AN: 1441482Hom.: 0 Cov.: 27 AF XY: 0.00000140 AC XY: 1AN XY: 715836 show subpopulations ⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
GnomAD4 exome
AF:
AC:
2
AN:
1441482
Hom.:
Cov.:
27
AF XY:
AC XY:
1
AN XY:
715836
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
AC:
0
AN:
32914
American (AMR)
AF:
AC:
0
AN:
43538
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25640
East Asian (EAS)
AF:
AC:
0
AN:
39278
South Asian (SAS)
AF:
AC:
0
AN:
84514
European-Finnish (FIN)
AF:
AC:
0
AN:
52492
Middle Eastern (MID)
AF:
AC:
0
AN:
5674
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1097968
Other (OTH)
AF:
AC:
0
AN:
59464
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0296732), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.400
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
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75-80
>80
Age
GnomAD4 genome 0.00000657 AC: 1AN: 152140Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74348 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152140
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
74348
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41528
American (AMR)
AF:
AC:
0
AN:
15264
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5152
South Asian (SAS)
AF:
AC:
1
AN:
4818
European-Finnish (FIN)
AF:
AC:
0
AN:
10590
Middle Eastern (MID)
AF:
AC:
0
AN:
294
European-Non Finnish (NFE)
AF:
AC:
0
AN:
67998
Other (OTH)
AF:
AC:
0
AN:
2114
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
La Branchor
BranchPoint Hunter
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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