Genetic Variant DLGAP2:p.Ile471Met (chr8-1565865-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001346810.2(DLGAP2):c.1413C>G(p.Ile471Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,448 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. I471I) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.795

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 links:

DLGAP2-AS1 (HGNC:50467): (DLGAP2 antisense RNA 1)

DLGAP2-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08722502).

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.1413C>G	p.Ile471Met	missense	Exon 6 of 15	NP_001333739.1	A0A1B0GTN4
	DLGAP2-AS1	NR_103863.1		n.358-127G>C		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.1413C>G	p.Ile471Met	missense	Exon 6 of 15	ENSP00000489774.1	A0A1B0GTN4
DLGAP2	ENST00000520901.5	TSL:1	c.1221C>G	p.Ile407Met	missense	Exon 2 of 10	ENSP00000430563.3	H0YBY6
DLGAP2	ENST00000421627.7	TSL:5	c.1410C>G	p.Ile470Met	missense	Exon 6 of 15	ENSP00000400258.3	Q9P1A6-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458448

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

725200

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33386

American (AMR)

AF:

0.00

AC:

AN:

44278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26080

East Asian (EAS)

AF:

0.0000253

AC:

AN:

39516

South Asian (SAS)

AF:

0.00

AC:

AN:

85548

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1110478

Other (OTH)

AF:

0.00

AC:

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.066

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.032

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.016

Eigen

Benign

-0.92

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.75

M_CAP

Benign

0.0060

MetaRNN

Benign

0.087

MetaSVM

Benign

-0.98

MutationAssessor

Benign

-0.40

PhyloP100

-0.80

PrimateAI

Benign

0.46

REVEL

Benign

0.087

Sift4G

Uncertain

0.028

Polyphen

0.57

Vest4

0.17

MutPred

0.13

Loss of catalytic residue at I470 (P = 0.0326)

MVP

0.17

MPC

0.10

ClinPred

0.42

GERP RS

-9.1

Varity_R

0.037

gMVP

0.23

Mutation Taster

=92/8

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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.

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