chr18-3502620-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_004746.4(DLGAP1):c.2597C>A(p.Thr866Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
DLGAP1
NM_004746.4 missense
NM_004746.4 missense
Scores
1
10
6
Clinical Significance
Conservation
PhyloP100: 5.37
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 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DLGAP1 | NM_004746.4 | c.2597C>A | p.Thr866Asn | missense_variant | 12/13 | ENST00000315677.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DLGAP1 | ENST00000315677.8 | c.2597C>A | p.Thr866Asn | missense_variant | 12/13 | 5 | NM_004746.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461788Hom.: 0 Cov.: 32 AF XY: 0.00000413 AC XY: 3AN XY: 727202
GnomAD4 exome
AF:
AC:
4
AN:
1461788
Hom.:
Cov.:
32
AF XY:
AC XY:
3
AN XY:
727202
Gnomad4 AFR exome
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Gnomad4 ASJ exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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Gnomad4 NFE exome
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Gnomad4 OTH exome
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
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 | Dec 21, 2023 | The c.2597C>A (p.T866N) alteration is located in exon 12 (coding exon 9) of the DLGAP1 gene. This alteration results from a C to A substitution at nucleotide position 2597, causing the threonine (T) at amino acid position 866 to be replaced by an asparagine (N). 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
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Pathogenic
D;D;.;D;D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;.;D;D;D;.;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;.;D;D;D;.;D;.
Sift4G
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Polyphen
P;.;.;.;.;P;.;.;.;P;.
Vest4
MutPred
0.76
.;.;.;.;.;Loss of phosphorylation at T866 (P = 0.0176);.;.;.;.;Loss of phosphorylation at T866 (P = 0.0176);
MVP
MPC
1.4
ClinPred
D
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
Publications
No publications associated with this variant yet.