20-36446907-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001365621.2(DLGAP4):c.1618G>A(p.Gly540Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000748 in 1,611,808 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00068 ( 4 hom. )

Consequence

DLGAP4
NM_001365621.2 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.04

Publications

4 publications found

Variant links:

Genes affected

DLGAP4 (HGNC:24476): (DLG associated protein 4) The product of this gene is a membrane-associated guanylate kinase found at the postsynaptic density in neuronal cells. It is a signaling molecule that can interact with potassium channels and receptors, as well as other signaling molecules. The protein encoded by this gene can interact with PSD-95 through its guanylate kinase domain and may be involved in clustering PSD-95 in the postsynaptic density region. The encoded protein is one of at least four similar proteins that have been found. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

DLGAP4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003807187).

BP6

Variant 20-36446907-G-A is Benign according to our data. Variant chr20-36446907-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 728931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 211 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP4	NM_001365621.2 link	c.1618G>A	p.Gly540Ser	missense_variant	Exon 7 of 13	ENST00000339266.10	NP_001352550.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
DLGAP4	ENST00000339266.10 link	c.1618G>A	p.Gly540Ser	missense_variant	Exon 7 of 13	5	NM_001365621.2	ENSP00000341633.5	Q9Y2H0-2
DLGAP4	ENST00000373913.7 link	c.1618G>A	p.Gly540Ser	missense_variant	Exon 7 of 13	1		ENSP00000363023.3	Q9Y2H0-1
DLGAP4	ENST00000373907.6 link	c.1618G>A	p.Gly540Ser	missense_variant	Exon 6 of 12	5		ENSP00000363014.2	Q9Y2H0-2

Frequencies

GnomAD3 genomes

AF:

0.00135

AC:

206

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00273

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00192

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000147

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.00125

AC:

312

AN:

249294

AF XY:

0.00135

show subpopulations

Gnomad AFR exome

AF:

0.00276

Gnomad AMR exome

AF:

0.000377

Gnomad ASJ exome

AF:

0.0157

Gnomad EAS exome

AF:

0.00224

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000231

Gnomad OTH exome

AF:

0.00296

GnomAD4 exome

AF:

0.000682

AC:

995

AN:

1459496

Hom.:

Cov.:

AF XY:

0.000694

AC XY:

504

AN XY:

725738

show subpopulations

African (AFR)

AF:

0.00347

AC:

116

AN:

33442

American (AMR)

AF:

0.000381

AC:

AN:

44664

Ashkenazi Jewish (ASJ)

AF:

0.0169

AC:

442

AN:

26104

East Asian (EAS)

AF:

0.00134

AC:

AN:

39650

South Asian (SAS)

AF:

0.000336

AC:

AN:

86196

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52652

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.000179

AC:

199

AN:

1110704

Other (OTH)

AF:

0.00220

AC:

133

AN:

60324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

117

176

234

293

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00139

AC:

211

AN:

152312

Hom.:

Cov.:

AF XY:

0.00145

AC XY:

108

AN XY:

74476

show subpopulations

African (AFR)

AF:

0.00284

AC:

118

AN:

41564

American (AMR)

AF:

0.000719

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

3470

East Asian (EAS)

AF:

0.00193

AC:

AN:

5184

South Asian (SAS)

AF:

0.000829

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000147

AC:

AN:

68034

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00136

Hom.:

Bravo

AF:

0.00150

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.00

AC:

ESP6500AA

AF:

0.00227

AC:

ESP6500EA

AF:

0.00105

AC:

ExAC

AF:

0.00104

AC:

126

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.000382

EpiControl

AF:

0.000237

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.73

DEOGEN2

Benign

0.0053

.;T;.;T

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.26

FATHMM_MKL

Uncertain

0.86

LIST_S2

Benign

0.77

.;T;T;.

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0038

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-1.4

N;N;N;N

PhyloP100

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

0.55

N;N;N;N

REVEL

Benign

0.043

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.63

T;T;T;T

Polyphen

0.030

B;.;B;.

Vest4

0.23

MVP

0.49

MPC

0.53

ClinPred

0.018

GERP RS

3.2

Varity_R

0.039

gMVP

0.15

Mutation Taster

=94/6

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

20-36446907-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over