Variant 8-1548707-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001346810.2(DLGAP2):c.254C>G(p.Ser85Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000187 in 1,607,280 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 Uncertain significance (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 5.76

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.31212154).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DLGAP2	NM_001346810.2 linkuse as main transcript	c.254C>G	p.Ser85Cys	missense_variant	5/15	ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2 linkuse as main transcript	c.254C>G	p.Ser85Cys	missense_variant	5/15	5	NM_001346810.2	ENSP00000489774
DLGAP2	ENST00000520901.5 linkuse as main transcript	c.65C>G	p.Ser22Cys	missense_variant	1/10	1		ENSP00000430563
DLGAP2	ENST00000421627.7 linkuse as main transcript	c.251C>G	p.Ser84Cys	missense_variant	5/15	5		ENSP00000400258		Q9P1A6-1
DLGAP2	ENST00000612087.1 linkuse as main transcript	c.14C>G	p.Ser5Cys	missense_variant	2/11	5		ENSP00000484215	P1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1455134

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723502

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:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.00000858

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLGAP2-related disorder

Uncertain:1

Uncertain significance, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Aug 26, 2024

The DLGAP2 c.254C>G variant is predicted to result in the amino acid substitution p.Ser85Cys. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.55

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

T;T;T

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.097

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.92

D;D;D

M_CAP

Benign

0.021

MetaRNN

Benign

0.31

T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.4

.;M;.

MutationTaster

Benign

0.98

PrimateAI

Uncertain

0.54

REVEL

Benign

0.14

Sift4G

Uncertain

0.033

.;.;D

Polyphen

0.94

.;P;.

Vest4

0.51

MutPred

0.20

.;Loss of phosphorylation at S84 (P = 0.0165);.;

MVP

0.19

MPC

0.29

ClinPred

0.87

GERP RS

4.8

Varity_R

0.13

gMVP

0.15

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