Variant 8-1548992-A-C 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.539A>C(p.His180Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000159 in 1,446,858 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/19 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: 0.000016 ( 0 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.67

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.215184).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP2	NM_001346810.2 linkuse as main transcript	c.539A>C	p.His180Pro	missense_variant	5/15	ENST00000637795.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP2	ENST00000637795.2 linkuse as main transcript	c.539A>C	p.His180Pro	missense_variant	5/15	5	NM_001346810.2
DLGAP2	ENST00000520901.5 linkuse as main transcript	c.350A>C	p.His117Pro	missense_variant	1/10	1
DLGAP2	ENST00000421627.7 linkuse as main transcript	c.536A>C	p.His179Pro	missense_variant	5/15	5			Q9P1A6-1
DLGAP2	ENST00000612087.1 linkuse as main transcript	c.299A>C	p.His100Pro	missense_variant	2/11	5		P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000439

AC:

AN:

227622

Hom.:

AF XY:

0.00000796

AC XY:

AN XY:

125626

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:

0.00000960

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000159

AC:

AN:

1446858

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

720242

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:

0.0000207

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000830

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 28, 2022

The c.299A>C (p.H100P) alteration is located in exon 2 (coding exon 1) of the DLGAP2 gene. This alteration results from a A to C substitution at nucleotide position 299, causing the histidine (H) at amino acid position 100 to be replaced by a proline (P). 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

0.057

BayesDel_addAF

Benign

-0.055

BayesDel_noAF

Benign

-0.32

Cadd

Benign

Dann

Benign

0.66

DEOGEN2

Benign

0.011

T;T;T

Eigen

Benign

-0.050

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.78

MutationTaster

Benign

0.71

PrimateAI

Uncertain

0.53

Polyphen

0.97

.;D;.

Vest4

0.81

MutPred

0.41

.;Loss of helix (P = 0.0304);.;

MVP

0.42

MPC

0.17

ClinPred

0.30

GERP RS

4.3

Varity_R

0.096

gMVP

0.36

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