Genetic Variant NM_001142699.3:c.40+144950C>A (chr11-85453707-G-T) – 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.40+144950C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 152,020 control chromosomes in the GnomAD database, including 13,867 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 0.42 ( 13862 hom., cov: 31)

Exomes 𝑓: 0.33 ( 5 hom. )

Consequence

DLG2
NM_001142699.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.45

Publications

12 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:

LOC100421303 (HGNC:):

LOC100421303 links:

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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=-0.57).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.538 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLG2	NM_001142699.3 link	c.40+144950C>A		intron_variant	Intron 3 of 27	ENST00000376104.7	NP_001136171.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLG2	ENST00000376104.7 link	c.40+144950C>A		intron_variant	Intron 3 of 27	1	NM_001142699.3	ENSP00000365272.2

Frequencies

GnomAD3 genomes

AF:

0.421

AC:

63898

AN:

151746

Hom.:

13856

Cov.:

show subpopulations

Gnomad AFR

AF:

0.349

Gnomad AMI

AF:

0.497

Gnomad AMR

AF:

0.361

Gnomad ASJ

AF:

0.491

Gnomad EAS

AF:

0.556

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.343

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.472

Gnomad OTH

AF:

0.441

GnomAD4 exome

AF:

0.333

AC:

AN:

156

Hom.:

Cov.:

AF XY:

0.321

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.333

AC:

AN:

150

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.250

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.421

AC:

63907

AN:

151864

Hom.:

13862

Cov.:

AF XY:

0.414

AC XY:

30740

AN XY:

74222

show subpopulations

African (AFR)

AF:

0.349

AC:

14445

AN:

41420

American (AMR)

AF:

0.360

AC:

5490

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.491

AC:

1705

AN:

3470

East Asian (EAS)

AF:

0.555

AC:

2864

AN:

5158

South Asian (SAS)

AF:

0.456

AC:

2189

AN:

4802

European-Finnish (FIN)

AF:

0.343

AC:

3619

AN:

10542

Middle Eastern (MID)

AF:

0.579

AC:

169

AN:

292

European-Non Finnish (NFE)

AF:

0.472

AC:

32044

AN:

67930

Other (OTH)

AF:

0.442

AC:

930

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1836

3672

5509

7345

9181

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

602

1204

1806

2408

3010

<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:

0.462

Hom.:

46672

Bravo

AF:

0.418

Asia WGS

AF:

0.464

AC:

1610

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.57

CADD

Benign

2.0

(source)

DANN

Benign

0.68

PhyloP100

2.5

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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