Variant 8-737814-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2

The NM_001346810.2(DLGAP2):c.7G>T(p.Ala3Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00993 in 379,658 control chromosomes in the GnomAD database, including 41 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.0089 ( 14 hom., cov: 33)

Exomes 𝑓: 0.011 ( 27 hom. )

Consequence

DLGAP2
NM_001346810.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.27

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:

ERICH1 (HGNC:27234): (glutamate rich 1)

ERICH1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004456252).

BP6

Variant 8-737814-G-T is Benign according to our data. Variant chr8-737814-G-T is described in ClinVar as [Benign]. Clinvar id is 3039242.Status of the report is no_assertion_criteria_provided, 0 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00888 (1345/151410) while in subpopulation SAS AF= 0.0321 (155/4834). AF 95% confidence interval is 0.0279. There are 14 homozygotes in gnomad4. There are 643 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 14 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DLGAP2	NM_001346810.2 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/15	ENST00000637795.2
DLGAP2	NR_073397.2 linkuse as main transcript	n.187G>T		non_coding_transcript_exon_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DLGAP2	ENST00000637795.2 linkuse as main transcript	c.7G>T	p.Ala3Ser	missense_variant	1/15	5	NM_001346810.2

Frequencies

GnomAD3 genomes

AF:

0.00888

AC:

1344

AN:

151302

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00208

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0103

Gnomad ASJ

AF:

0.00636

Gnomad EAS

AF:

0.000973

Gnomad SAS

AF:

0.0318

Gnomad FIN

AF:

0.00496

Gnomad MID

AF:

0.0191

Gnomad NFE

AF:

0.0124

Gnomad OTH

AF:

0.0106

GnomAD4 exome

AF:

0.0106

AC:

2425

AN:

228248

Hom.:

Cov.:

AF XY:

0.0110

AC XY:

1277

AN XY:

116330

show subpopulations

Gnomad4 AFR exome

AF:

0.00316

Gnomad4 AMR exome

AF:

0.00737

Gnomad4 ASJ exome

AF:

0.00538

Gnomad4 EAS exome

AF:

0.0000464

Gnomad4 SAS exome

AF:

0.0303

Gnomad4 FIN exome

AF:

0.00694

Gnomad4 NFE exome

AF:

0.0130

Gnomad4 OTH exome

AF:

0.0104

GnomAD4 genome

AF:

0.00888

AC:

1345

AN:

151410

Hom.:

Cov.:

AF XY:

0.00869

AC XY:

643

AN XY:

73980

show subpopulations

Gnomad4 AFR

AF:

0.00207

Gnomad4 AMR

AF:

0.0103

Gnomad4 ASJ

AF:

0.00636

Gnomad4 EAS

AF:

0.000976

Gnomad4 SAS

AF:

0.0321

Gnomad4 FIN

AF:

0.00496

Gnomad4 NFE

AF:

0.0124

Gnomad4 OTH

AF:

0.0105

Alfa

AF:

0.00295

Hom.:

Bravo

AF:

0.00829

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DLGAP2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.0068

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0045

GERP RS

1.7

gMVP

0.021

Splicing

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