chr8-1532799-A-C

Variant names:

• chr8-1532799-A-C
• rs17748677
• NM_001346810.2:c.173-15827A>C

Variant summary

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

The NM_001346810.2(DLGAP2):​c.173-15827A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,236 control chromosomes in the GnomAD database, including 1,763 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 0.14 (1763 hom., cov: 32)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628
• Publications: 4 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 = 0.26 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.173-15827A>C		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.173-15827A>C		intron	N/A	ENSP00000489774.1
	DLGAP2	ENST00000421627.7	TSL:5	c.170-15827A>C		intron	N/A	ENSP00000400258.3
	DLGAP2	ENST00000612087.1	TSL:5	c.-68-15827A>C		intron	N/A	ENSP00000484215.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20648 AN: 152116 Hom.: 1766 Cov.: 32

Gnomad AFR AF: 0.0353

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.155

Gnomad ASJ AF: 0.101

Gnomad EAS AF: 0.272

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.146

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.177

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.136 AC: 20644 AN: 152236 Hom.: 1763 Cov.: 32 AF XY: 0.137 AC XY: 10229 AN XY: 74430

African (AFR) AF: 0.0352 AC: 1461 AN: 41554

American (AMR) AF: 0.154 AC: 2363 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 352 AN: 3472

East Asian (EAS) AF: 0.272 AC: 1404 AN: 5168

South Asian (SAS) AF: 0.218 AC: 1050 AN: 4812

European-Finnish (FIN) AF: 0.146 AC: 1545 AN: 10604

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.177 AC: 12062 AN: 68010

Other (OTH) AF: 0.138 AC: 291 AN: 2116

Alfa AF: 0.160 Hom.: 6961

Bravo AF: 0.133

Asia WGS AF: 0.234 AC: 811 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.7
DANN	Benign	0.57
PhyloP100		0.63
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

Other links and lift over

dbSNP: rs17748677; hg19: chr8-1480965;