rs17669535

Variant names:

• chr8-1295964-C-G
• rs17669535
• NM_001346810.2:c.106+37081C>G

Variant summary

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

The NM_001346810.2(DLGAP2):​c.106+37081C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0765 in 152,270 control chromosomes in the GnomAD database, including 608 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 0.076 (608 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: DLGAP2 NM_001346810.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.732
• Publications: 7 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

ENSG00000275427 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.16 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.106+37081C>G		intron	N/A	NP_001333739.1
	LOC286083	NR_111948.1		n.*70G>C		downstream_gene	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DLGAP2	ENST00000637795.2	TSL:5 MANE Select	c.106+37081C>G		intron	N/A	ENSP00000489774.1
	DLGAP2	ENST00000421627.7	TSL:5	c.103+37081C>G		intron	N/A	ENSP00000400258.3
	ENSG00000275427	ENST00000617093.1	TSL:1	n.*70G>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0766 AC: 11657 AN: 152148 Hom.: 610 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0676

Gnomad ASJ AF: 0.0942

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0962

Gnomad MID AF: 0.0696

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.0860

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.0765 AC: 11642 AN: 152266 Hom.: 608 Cov.: 33 AF XY: 0.0789 AC XY: 5874 AN XY: 74446

African (AFR) AF: 0.0182 AC: 758 AN: 41570

American (AMR) AF: 0.0674 AC: 1031 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0942 AC: 327 AN: 3472

East Asian (EAS) AF: 0.142 AC: 734 AN: 5174

South Asian (SAS) AF: 0.169 AC: 817 AN: 4822

European-Finnish (FIN) AF: 0.0962 AC: 1020 AN: 10604

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.0987 AC: 6711 AN: 68014

Other (OTH) AF: 0.0837 AC: 177 AN: 2114

Alfa AF: 0.0789 Hom.: 68

Bravo AF: 0.0699

Asia WGS AF: 0.123 AC: 431 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.5
DANN	Benign	0.53
PhyloP100		0.73

Splicing

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

Other links and lift over

dbSNP: rs17669535; hg19: chr8-1244224;