chr8-1425554-G-A

Variant names:

• chr8-1425554-G-A
• rs28680850
• NM_001346810.2:c.107-75812G>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.107-75812G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.226 in 152,100 control chromosomes in the GnomAD database, including 5,108 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 0.23 (5108 hom., cov: 33)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.330
• Publications: 6 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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.527 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DLGAP2	NM_001346810.2	c.107-75812G>A		intron_variant	Intron 3 of 14	ENST00000637795.2	NP_001333739.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DLGAP2	ENST00000637795.2	c.107-75812G>A		intron_variant	Intron 3 of 14	5	NM_001346810.2	ENSP00000489774.1
DLGAP2	ENST00000421627.7	c.104-75812G>A		intron_variant	Intron 3 of 14	5		ENSP00000400258.3

Frequencies

GnomAD3 genomes AF: 0.226 AC: 34321 AN: 151982 Hom.: 5100 Cov.: 33

Gnomad AFR AF: 0.0697

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.373

Gnomad ASJ AF: 0.255

Gnomad EAS AF: 0.543

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.337

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.232

Gnomad OTH AF: 0.223

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

GnomAD4 genome AF: 0.226 AC: 34338 AN: 152100 Hom.: 5108 Cov.: 33 AF XY: 0.238 AC XY: 17651 AN XY: 74310

African (AFR) AF: 0.0696 AC: 2893 AN: 41544

American (AMR) AF: 0.374 AC: 5716 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.255 AC: 884 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2784 AN: 5118

South Asian (SAS) AF: 0.430 AC: 2068 AN: 4814

European-Finnish (FIN) AF: 0.337 AC: 3566 AN: 10572

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.232 AC: 15754 AN: 67982

Other (OTH) AF: 0.222 AC: 468 AN: 2112

Alfa AF: 0.243 Hom.: 8211

Bravo AF: 0.223

Asia WGS AF: 0.458 AC: 1589 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.4
DANN	Benign	0.45
PhyloP100		-0.33

Splicing

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

Other links and lift over

dbSNP: rs28680850; hg19: chr8-1373720;