Genetic Variant NM_001142699.3:c.1057-75G>C (chr11-83965543-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001142699.3(DLG2):c.1057-75G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.125 in 1,217,834 control chromosomes in the GnomAD database, including 10,967 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.098 ( 940 hom., cov: 32)

Exomes 𝑓: 0.13 ( 10027 hom. )

Consequence

DLG2
NM_001142699.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.50

Publications

4 publications found

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]

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

DLG2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3 link	c.1057-75G>C		intron_variant	Intron 12 of 27	ENST00000376104.7	NP_001136171.1	Q15700-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7 link	c.1057-75G>C		intron_variant	Intron 12 of 27	1	NM_001142699.3	ENSP00000365272.2		Q15700-2

Frequencies

GnomAD3 genomes

AF:

0.0979

AC:

14857

AN:

151754

Hom.:

943

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0270

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.158

Gnomad ASJ

AF:

0.0933

Gnomad EAS

AF:

0.0216

Gnomad SAS

AF:

0.153

Gnomad FIN

AF:

0.0689

Gnomad MID

AF:

0.0669

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.0879

GnomAD4 exome

AF:

0.129

AC:

137510

AN:

1065962

Hom.:

10027

AF XY:

0.129

AC XY:

69621

AN XY:

538112

show subpopulations

African (AFR)

AF:

0.0189

AC:

447

AN:

23616

American (AMR)

AF:

0.212

AC:

5983

AN:

28246

Ashkenazi Jewish (ASJ)

AF:

0.0983

AC:

1813

AN:

18442

East Asian (EAS)

AF:

0.0117

AC:

427

AN:

36362

South Asian (SAS)

AF:

0.142

AC:

9071

AN:

63864

European-Finnish (FIN)

AF:

0.0762

AC:

3527

AN:

46286

Middle Eastern (MID)

AF:

0.0749

AC:

257

AN:

3432

European-Non Finnish (NFE)

AF:

0.138

AC:

110665

AN:

799416

Other (OTH)

AF:

0.115

AC:

5320

AN:

46298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.509

Heterozygous variant carriers

5791

11581

17372

23162

28953

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3638

7276

10914

14552

18190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0978

AC:

14860

AN:

151872

Hom.:

940

Cov.:

AF XY:

0.0963

AC XY:

7151

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.0269

AC:

1116

AN:

41484

American (AMR)

AF:

0.158

AC:

2401

AN:

15206

Ashkenazi Jewish (ASJ)

AF:

0.0933

AC:

323

AN:

3462

East Asian (EAS)

AF:

0.0217

AC:

112

AN:

5172

South Asian (SAS)

AF:

0.154

AC:

743

AN:

4822

European-Finnish (FIN)

AF:

0.0689

AC:

730

AN:

10588

Middle Eastern (MID)

AF:

0.0548

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.136

AC:

9199

AN:

67830

Other (OTH)

AF:

0.0879

AC:

185

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

690

1379

2069

2758

3448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

178

356

534

712

890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.123

Hom.:

166

Bravo

AF:

0.0981

Asia WGS

AF:

0.0880

AC:

306

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.68

(source)

DANN

Benign

0.42

PhyloP100

-1.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over