18-3534521-C-G
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate
The NM_004746.4(DLGAP1):c.2152G>C(p.Glu718Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,154 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Consequence
DLGAP1
NM_004746.4 missense
NM_004746.4 missense
Scores
1
4
12
Clinical Significance
Conservation
PhyloP100: 4.70
Genes affected
DLGAP1 (HGNC:2905): (DLG associated protein 1) Predicted to enable molecular adaptor activity. Predicted to be a structural constituent of postsynaptic density. Predicted to be involved in several processes, including aggresome assembly; regulation of postsynaptic neurotransmitter receptor activity; and regulation of proteasomal protein catabolic process. Predicted to be located in plasma membrane. Predicted to be part of postsynaptic density. Predicted to be active in glutamatergic synapse and postsynaptic density, intracellular component. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.22081193).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLGAP1 | NM_004746.4 | c.2152G>C | p.Glu718Gln | missense_variant | 10/13 | ENST00000315677.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLGAP1 | ENST00000315677.8 | c.2152G>C | p.Glu718Gln | missense_variant | 10/13 | 5 | NM_004746.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251310Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135812
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GnomAD4 exome Cov.: 33
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152154Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
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ESP6500AA
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 23, 2021 | The c.2152G>C (p.E718Q) alteration is located in exon 10 (coding exon 7) of the DLGAP1 gene. This alteration results from a G to C substitution at nucleotide position 2152, causing the glutamic acid (E) at amino acid position 718 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;.;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N;.;N;N;N;.;N;.
REVEL
Benign
Sift
Benign
T;T;T;T;.;T;T;T;.;T;.
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T
Polyphen
B;.;.;.;.;B;.;.;.;B;.
Vest4
MVP
MPC
1.3
ClinPred
T
GERP RS
Varity_R
gMVP
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