dbSNP rs546907591: DLGAP2:p.Leu12Leu (chr8-907927-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6BP7BS2

The NM_001346810.2(DLGAP2):c.34C>T(p.Leu12Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 398,978 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 34)

Exomes 𝑓: 0.00036 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.97

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.19).

BP6

Variant 8-907927-C-T is Benign according to our data. Variant chr8-907927-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3044500.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=1.97 with no splicing effect.

BS2

High AC in GnomAd4 at 49 AD gene.

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.34C>T	p.Leu12Leu	synonymous	Exon 2 of 15	NP_001333739.1	A0A1B0GTN4
	DLGAP2	NR_073397.2		n.316C>T		non_coding_transcript_exon	Exon 3 of 4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.34C>T	p.Leu12Leu	synonymous	Exon 2 of 15	ENSP00000489774.1	A0A1B0GTN4
DLGAP2	ENST00000522092.5	TSL:1	n.293C>T		non_coding_transcript_exon	Exon 3 of 4
DLGAP2	ENST00000524139.5	TSL:1	n.167C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000193

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000338

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000361

AC:

AN:

246630

Hom.:

Cov.:

AF XY:

0.000320

AC XY:

AN XY:

124984

show subpopulations

African (AFR)

AF:

0.000139

AC:

AN:

7180

American (AMR)

AF:

0.000673

AC:

AN:

7434

Ashkenazi Jewish (ASJ)

AF:

0.00336

AC:

AN:

9238

East Asian (EAS)

AF:

0.00

AC:

AN:

22886

South Asian (SAS)

AF:

0.00

AC:

AN:

3028

European-Finnish (FIN)

AF:

0.0000944

AC:

AN:

21178

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.000272

AC:

AN:

158020

Other (OTH)

AF:

0.000428

AC:

AN:

16372

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

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:

0.000322

AC:

AN:

152348

Hom.:

Cov.:

AF XY:

0.000282

AC XY:

AN XY:

74498

show subpopulations

African (AFR)

AF:

0.000192

AC:

AN:

41584

American (AMR)

AF:

0.000196

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000338

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000582

Hom.:

Bravo

AF:

0.000332

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

DLGAP2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.19

CADD

Benign

(source)

DANN

Benign

0.91

PhyloP100

2.0

Mutation Taster

=99/1

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over