11-83471718-G-C

Variant names:

• chr11-83471718-G-C
• rs777007201
• NM_001142699.3:c.2354C>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001142699.3(DLG2):​c.2354C>G​(p.Thr785Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000479 in 1,460,516 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T785I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: DLG2 NM_001142699.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.04
• Publications: 4 publications found

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]

DLG2 Gene-Disease associations (from GenCC):

• delayed puberty, self-limited

  Inheritance: AD, AR Classification: LIMITED Submitted by: Ambry Genetics
• neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3103506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3	c.2354C>G	p.Thr785Ser	missense_variant	Exon 24 of 28	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7	c.2354C>G	p.Thr785Ser	missense_variant	Exon 24 of 28	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000403 AC: 1 AN: 248224 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000890

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1460516 Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3 AN XY: 726558

African (AFR) AF: 0.00 AC: 0 AN: 33410

American (AMR) AF: 0.00 AC: 0 AN: 44614

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.00 AC: 0 AN: 86182

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.000694 AC: 4 AN: 5764

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111112

Other (OTH) AF: 0.0000166 AC: 1 AN: 60314

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.082	T
BayesDel_noAF	Benign	-0.36
CADD	Pathogenic	26
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.52	.;D;.;.;.;.;.;T;T;T;T;.;T
Eigen	Benign	0.063
Eigen_PC	Benign	0.17
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.79	T;T;T;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.31	T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	1.0	.;L;.;.;.;.;.;.;.;.;.;.;.
PhyloP100		8.0
PrimateAI	Uncertain	0.71	T
PROVEAN	Benign	-2.0	N;N;N;.;.;N;N;D;N;N;N;D;D
REVEL	Benign	0.14
Sift	Benign	0.11	T;T;T;.;.;T;T;T;T;T;T;T;T
Sift4G	Benign	0.15	T;T;T;.;.;T;T;T;T;T;T;.;.
Polyphen		0.022, 0.46, 0.011, 0.0070, 0.067, 0.42	.;B;.;.;.;P;B;B;B;B;B;.;.
Vest4		0.45
MutPred		0.42		.;Loss of sheet (P = 0.0315);.;.;.;.;.;.;.;.;.;.;.;
MVP		0.52
MPC		0.94
ClinPred		0.64	D
GERP RS		5.1
Varity_R		0.18
gMVP		0.84
Mutation Taster		=71/29	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs777007201; hg19: chr11-83182761;