11-83469205-T-C
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000376104.7(DLG2):āc.2615A>Gā(p.Glu872Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000374 in 1,604,586 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000034 ( 0 hom. )
Consequence
DLG2
ENST00000376104.7 missense
ENST00000376104.7 missense
Scores
8
7
4
Clinical Significance
Conservation
PhyloP100: 7.67
Genes affected
DLG2 (HGNC:2901): (discs large MAGUK scaffold protein 2) This gene encodes a member of the membrane-associated guanylate kinase (MAGUK) family. The encoded protein forms a heterodimer with a related family member that may interact at postsynaptic sites to form a multimeric scaffold for the clustering of receptors, ion channels, and associated signaling proteins. Multiple transcript variants encoding different isoforms have been found for this gene. Additional transcript variants have been described, but their full-length nature is not known. [provided by RefSeq, Dec 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 5 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
DLG2 | NM_001142699.3 | c.2615A>G | p.Glu872Gly | missense_variant | 25/28 | ENST00000376104.7 | NP_001136171.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
DLG2 | ENST00000376104.7 | c.2615A>G | p.Glu872Gly | missense_variant | 25/28 | 1 | NM_001142699.3 | ENSP00000365272 |
Frequencies
GnomAD3 genomes AF: 0.00000658 AC: 1AN: 152042Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000247 AC: 6AN: 243150Hom.: 0 AF XY: 0.0000227 AC XY: 3AN XY: 132140
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GnomAD4 exome AF: 0.00000344 AC: 5AN: 1452428Hom.: 0 Cov.: 32 AF XY: 0.00000277 AC XY: 2AN XY: 722208
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152158Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74368
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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 | May 20, 2024 | The c.2615A>G (p.E872G) alteration is located in exon 25 (coding exon 23) of the DLG2 gene. This alteration results from a A to G substitution at nucleotide position 2615, causing the glutamic acid (E) at amino acid position 872 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Benign
.;T;.;.;.;.;.;T;T;T;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
D
MetaRNN
Uncertain
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Uncertain
.;M;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;D;D;.;.;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;.;.;D;D;D;D;D;D;D
Sift4G
Benign
T;T;T;.;.;T;T;T;T;T;T;.
Polyphen
0.97, 1.0, 1.0, 0.98, 0.97
.;D;.;.;.;D;D;D;D;D;D;.
Vest4
MutPred
0.49
.;Gain of catalytic residue at A766 (P = 0.0205);.;.;.;.;.;.;.;.;.;.;
MVP
MPC
1.8
ClinPred
D
GERP RS
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gMVP
Splicing
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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