rs4418368

Variant names:

• chr8-1650212-G-A
• rs4418368
• NM_001346810.2:c.1810+17166G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001346810.2(DLGAP2):​c.1810+17166G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 152,074 control chromosomes in the GnomAD database, including 8,807 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.34 (8807 hom., cov: 33)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0100
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

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.1810+17166G>A		intron	N/A	NP_001333739.1	A0A1B0GTN4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.1810+17166G>A		intron	N/A	ENSP00000489774.1	A0A1B0GTN4
	DLGAP2	ENST00000520901.5	TSL:1	c.1618+17166G>A		intron	N/A	ENSP00000430563.3	H0YBY6
	DLGAP2	ENST00000421627.7	TSL:5	c.1807+17166G>A		intron	N/A	ENSP00000400258.3	Q9P1A6-1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51703 AN: 151954 Hom.: 8796 Cov.: 33

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.254

Gnomad AMR AF: 0.324

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.339

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.398

Gnomad MID AF: 0.386

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.344

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.340 AC: 51751 AN: 152074 Hom.: 8807 Cov.: 33 AF XY: 0.343 AC XY: 25518 AN XY: 74342

African (AFR) AF: 0.336 AC: 13944 AN: 41454

American (AMR) AF: 0.324 AC: 4948 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 1021 AN: 3472

East Asian (EAS) AF: 0.339 AC: 1750 AN: 5166

South Asian (SAS) AF: 0.273 AC: 1319 AN: 4826

European-Finnish (FIN) AF: 0.398 AC: 4207 AN: 10576

Middle Eastern (MID) AF: 0.388 AC: 114 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23498 AN: 67980

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.342 Hom.: 2955

Bravo AF: 0.334

Asia WGS AF: 0.291 AC: 1013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.4
DANN	Benign	0.58
PhyloP100		0.010
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4418368;

hg19: chr8-1598378;