Variant chr8-1565867-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001346810.2(DLGAP2):c.1415G>A(p.Gly472Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000013 in 1,458,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.19

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0867483).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2 link	c.1415G>A	p.Gly472Glu	missense_variant	6/15	ENST00000637795.2	NP_001333739.1	A0A1B0GTN4
DLGAP2-AS1	NR_103863.1 link	n.358-129C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2 link	c.1415G>A	p.Gly472Glu	missense_variant	6/15	5	NM_001346810.2	ENSP00000489774.1		A0A1B0GTN4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000165

AC:

AN:

242054

Hom.:

AF XY:

0.0000229

AC XY:

AN XY:

131220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000366

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1458034

Hom.:

Cov.:

AF XY:

0.0000166

AC XY:

AN XY:

724932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.00000378

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000248

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 19, 2022

The c.1175G>A (p.G392E) alteration is located in exon 3 (coding exon 2) of the DLGAP2 gene. This alteration results from a G to A substitution at nucleotide position 1175, causing the glycine (G) at amino acid position 392 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Benign

0.77

DEOGEN2

Benign

0.012

T;T;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.61

FATHMM_MKL

Benign

0.62

LIST_S2

Benign

0.83

T;T;T

M_CAP

Benign

0.042

MetaRNN

Benign

0.087

T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

1.7

.;L;.

PrimateAI

Benign

0.47

REVEL

Benign

0.094

Sift4G

Benign

0.93

.;.;T

Polyphen

0.090

.;B;.

Vest4

0.30

MVP

0.26

MPC

0.14

ClinPred

0.099

GERP RS

2.5

Varity_R

0.047

gMVP

0.30

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over