dbSNP rs769477449: DLGAP2:p.Asp58Glu (chr8-1548627-C-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_001346810.2(DLGAP2):c.174C>A(p.Asp58Glu) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000292 in 1,371,594 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/16 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. D58D) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense, splice_region

Scores

Splicing: ADA: 0.0002928

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.564

Publications

0 publications found

Variant links:

Genes affected

DLGAP2 (HGNC:2906): (DLG associated protein 2) The product of this gene is a membrane-associated protein that may play a role in synapse organization and signalling in neuronal cells. This gene is biallelically expressed in the brain, however, only the paternal allele is expressed in the testis (PMID:18055845). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jun 2014]

DLGAP2 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

DLGAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.29267597).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001346810.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	NM_001346810.2	MANE Select	c.174C>A	p.Asp58Glu	missense splice_region	Exon 5 of 15	NP_001333739.1	A0A1B0GTN4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.174C>A	p.Asp58Glu	missense splice_region	Exon 5 of 15	ENSP00000489774.1	A0A1B0GTN4
DLGAP2	ENST00000421627.7	TSL:5	c.171C>A	p.Asp57Glu	missense splice_region	Exon 5 of 15	ENSP00000400258.3	Q9P1A6-1
DLGAP2	ENST00000612087.1	TSL:5	c.-67C>A		splice_region	Exon 2 of 11	ENSP00000484215.1	A0A1B0GXK6

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000292

AC:

AN:

1371594

Hom.:

Cov.:

AF XY:

0.00000446

AC XY:

AN XY:

673330

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30782

American (AMR)

AF:

0.00

AC:

AN:

34270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22340

East Asian (EAS)

AF:

0.00

AC:

AN:

37436

South Asian (SAS)

AF:

0.00

AC:

AN:

75574

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39732

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5472

European-Non Finnish (NFE)

AF:

0.00000374

AC:

AN:

1069092

Other (OTH)

AF:

0.00

AC:

AN:

56896

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Benign

0.86

DEOGEN2

Benign

0.016

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.83

LIST_S2

Benign

0.56

MetaRNN

Benign

0.29

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.9

PhyloP100

0.56

GERP RS

1.7

PromoterAI

0.031

Neutral

(source)

Varity_R

0.080

gMVP

0.21

Mutation Taster

=290/10

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00029

dbscSNV1_RF

Benign

0.0020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over