8-1144105-G-T

Variant names:

• chr8-1144105-G-T
• rs10046782
• NM_001346810.2:c.74-114746G>T

Variant summary

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

The NM_001346810.2(DLGAP2):​c.74-114746G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.341 in 152,142 control chromosomes in the GnomAD database, including 10,281 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 (10281 hom., cov: 33)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.314
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.441 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	NM_001346810.2	MANE Select	c.74-114746G>T		intron	N/A	NP_001333739.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.74-114746G>T		intron	N/A	ENSP00000489774.1
	DLGAP2	ENST00000421627.7	TSL:5	c.71-114746G>T		intron	N/A	ENSP00000400258.3
	DLGAP2	ENST00000520524.5	TSL:3	n.185+39039G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51855 AN: 152024 Hom.: 10280 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.552

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.436

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.350

Gnomad FIN AF: 0.429

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.341 AC: 51869 AN: 152142 Hom.: 10281 Cov.: 33 AF XY: 0.341 AC XY: 25345 AN XY: 74370

African (AFR) AF: 0.143 AC: 5954 AN: 41512

American (AMR) AF: 0.378 AC: 5783 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.436 AC: 1512 AN: 3468

East Asian (EAS) AF: 0.151 AC: 779 AN: 5174

South Asian (SAS) AF: 0.352 AC: 1696 AN: 4822

European-Finnish (FIN) AF: 0.429 AC: 4533 AN: 10576

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.445 AC: 30281 AN: 67988

Other (OTH) AF: 0.351 AC: 739 AN: 2108

Alfa AF: 0.408 Hom.: 21375

Bravo AF: 0.328

Asia WGS AF: 0.225 AC: 782 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.39
DANN	Benign	0.68
PhyloP100		-0.31

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10046782; hg19: chr8-1094105;