11-83469205-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000376104.7(DLG2):ā€‹c.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

Scores

8
7
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.67
Variant links:
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]

Genome browser will be placed here

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
DLG2NM_001142699.3 linkuse as main transcriptc.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
DLG2ENST00000376104.7 linkuse as main transcriptc.2615A>G p.Glu872Gly missense_variant 25/281 NM_001142699.3 ENSP00000365272 Q15700-2

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
152042
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000247
AC:
6
AN:
243150
Hom.:
0
AF XY:
0.0000227
AC XY:
3
AN XY:
132140
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000341
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000344
AC:
5
AN:
1452428
Hom.:
0
Cov.:
32
AF XY:
0.00000277
AC XY:
2
AN XY:
722208
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000127
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152158
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74368
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000194
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000189
ExAC
AF:
0.0000331
AC:
4

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 submitterclinical testingAmbry GeneticsMay 20, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.55
BayesDel_addAF
Uncertain
0.079
D
BayesDel_noAF
Pathogenic
0.18
CADD
Pathogenic
31
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.32
.;T;.;.;.;.;.;T;T;T;T;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.78
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Pathogenic
0.98
D;D;D;D;D;D;D;D;D;D;D;D
M_CAP
Uncertain
0.12
D
MetaRNN
Uncertain
0.73
D;D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Benign
-0.30
T
MutationAssessor
Uncertain
2.7
.;M;.;.;.;.;.;.;.;.;.;.
MutationTaster
Benign
1.0
D;D;D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
0.72
T
PROVEAN
Pathogenic
-5.9
D;D;D;.;.;D;D;D;D;D;D;D
REVEL
Pathogenic
0.65
Sift
Uncertain
0.0030
D;D;D;.;.;D;D;D;D;D;D;D
Sift4G
Benign
0.064
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
0.86
MutPred
0.49
.;Gain of catalytic residue at A766 (P = 0.0205);.;.;.;.;.;.;.;.;.;.;
MVP
0.82
MPC
1.8
ClinPred
0.87
D
GERP RS
5.7
Varity_R
0.61
gMVP
0.90

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.13
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs528157226; hg19: chr11-83180248; API